Insecticidal 3-(2,6-disubstituted phenyl)-5-[5-arylthien-2-yl]-1,2,4-triazoles

ABSTRACT

Triazole compounds having a 2,6-disubstituted-phenyl group in the 3-position, 5′-arylthien-2-yl group in the 5-position and an alkyl group in the 1-position are effective in controlling lepidoptera, coleoptera, mites and other sucking pests.

BACKGROUND OF THE INVENTION

[0001] This application is a division of application Ser. No. 10/244,124filed on Sep. 13, 2002. This application claims the benefit of U.S.Provisional Application No. 60/322,236, filed Sep. 14, 2001.

[0002] The present invention concerns novel 3-(2,6-disubstitutedphenyl)-5-(4- or 5-arylthien-2- or -3-yl)-1,2,4-triazoles and their usein controlling lepidoptera, coleoptera, mites and other sucking pests.This invention also includes new synthetic procedures, intermediates forpreparing the compounds, pesticide compositions containing thecompounds, and methods of controlling lepidoptera, coleoptera, mites andsucking pests using the compounds.

[0003] There is an acute need for new insecticides and acaricides.Insects and mites are developing resistance to the insecticides andacaricides in current use. At least 400 species of arthropods areresistant to one or more insecticides. The development of resistance tosome of the older insecticides, such as DDT, the carbamates, and theorganophosphates, is well known. But resistance has even developed tosome of the newer pyrethroid insecticides and acaricides. Therefore aneed exists for new insecticides and acaricides, and particularly forcompounds that have new or a typical modes of action.

[0004] A number of 3,5-diphenyl-1H-1,2,4-triazole derivatives have beendescribed in the literature as having acaricidal activity (U.S. Pat. No.5,482,951; JP 8092224, EP 572142, JP 08283261). U.S. Pat. No. 6,015,826discloses certain 3-(substituted phenyl)-5-(thienyl)-1,2,4-triazoles andtheir use in controlling certain insects and mites, viz., aphids, mitesand whiteflies. The present invention provides novel compounds withbroad-spectrum activity against lepidoptera and coleoptera in additionto mites and other sucking pests.

SUMMARY OF THE INVENTION

[0005] This invention concerns compounds especially useful for thecontrol of lepidoptera, coleoptera, mites and other sucking pests. Morespecifically, the invention concerns compounds of the formula (1)

[0006] wherein

[0007] Q represents

[0008] X and Y independently represent Cl or F;

[0009] R¹ and R² independently represent H, C₁-C₆ alkyl or halogen,provided that when Q is Q¹ or Q³, then R¹ and R² are not both H;

[0010] R³ represents C₁-C₃ alkyl;

[0011] R⁴ represents halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, C₁-C₆thioalkyl, C₃-C₆ alkoxyalkoxy, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, C₁-C₆halothioalkyl, C₃-C₆ alkenyloxy, or phenoxy;

[0012] R⁵ represents H, halogen or a C₁-C₆ alkyl ether or haloalkylether, which, when taken together with R⁴, forms a 5- or 6-membered ringcontaining 1 or 2 oxygen atoms;

[0013] or a phytologically acceptable acid addition salt thereof.

[0014] Preferred compounds of formula (1) include the following classes:

[0015] (1) Compounds of formula (1) wherein X and Y are both F.

[0016] (2) Compounds of formula (1) wherein X and Y are both Cl.

[0017] (3) Compounds of formula (1) wherein X is F and Y is Cl (morepreferred).

[0018] (4) Compounds of formula (1) wherein Q is Q¹ or Q³.

[0019] (5) Compounds of formula (1) wherein Q is Q².

[0020] (6) Compounds of formula (1) wherein R¹ is CH₃, CH₂CH₃ or Cl whenQ is Q¹ or Q³, more preferably R¹ is CH₃.

[0021] (7) Compounds of formula (1) wherein R¹ is H, CH₃, CH₂CH₃, Cl orBr when Q is Q², more preferably R¹ is H or CH₃.

[0022] (8) Compounds of formula (1) wherein R² is H, CH₃, CH₂CH₃, Cl orBr, more preferably R² is H or CH₃.

[0023] (9) Compounds of formula (1) wherein R⁴ is F, Cl, CF₃, haloalkoxyor phenoxy, more preferably R⁴ is haloalkoxy.

[0024] (10) Compounds of formula (1) wherein R⁴ is in the 4-position ofthe phenyl ring.

[0025] (11) Compounds of formula (1) wherein R⁵ is H, F, Cl, or CF₃.

[0026] (12) Compounds of formula (1) wherein R³ is CH₃.

[0027] It will be appreciated by those skilled in the art that the mostpreferred compounds are generally those which are comprised ofcombinations of the above preferred classes.

[0028] The invention also provides new processes and intermediates forpreparing compounds of formula (1) as well as new compositions andmethods of use, which will be described in detail hereinafter.

DETAILED DESCRIPTION OF THE INVENTION

[0029] Throughout this document, all temperatures are given in degreesCelsius, and all percentages are weight percentages unless otherwisestated.

[0030] Unless specifically limited otherwise, the terms “alkyl” and“alkenyl”, as well as derivative terms such as “alkoxy”, “alkenyloxy”and “thioalkyl”, as used herein, include within their scope straightchain, branched chain and cyclic moieties. The term “alkenyl” isintended to include one or more unsaturated bonds.

[0031] Unless specifically limited otherwise, the term “halogen”, aswell as derivative terms such as “halo”, as used herein, refers tofluorine, chlorine, bromine, and iodine. Preferred halogens are fluorineand chlorine.

[0032] The terms “haloalkyl” and “haloalkenyl” refer to alkyl andalkenyl groups substituted with from one up to the maximum possiblenumber of halogen atoms. The terms “haloalkoxy” and “halothioalkyl”refer to alkoxy and thioalkyl groups substituted with from one up to themaximum possible number of halogen atoms.

[0033] The term “alkoxyalkoxy” refers to an alkoxy group substitutedwith an alkoxy group. The term “alkyl ether” refers to an alkylene oxidegroup which can be bonded either through the carbon or the oxygen atom.

[0034] Unless otherwise indicated, when it is stated that a group may besubstituted with one or more substituents selected from an identifiedclass, it is intended that the substituents may be independentlyselected from the class.

[0035] Synthesis

[0036] Compounds of formula (1) can be prepared by the methodsillustrated in Scheme A:

[0037] wherein X, Y, R¹, R², R³, R⁴ and R⁵ are defined as in formula(1).

[0038] In step a of Scheme A, the compound of formula (A) is coupledwith the acid chloride of formula (B) to provide acyl thioimidate offormula (C). Pyridine is the preferred base for coupling, however anyorganic or inorganic base can be used. Acid chlorides of formula (B) areprepared from corresponding carboxylic acids of formula (G)

[0039] which are either commercially available or are readily madethrough known procedures.

[0040] Thioimidates (A) are readily available through alkylation of thecorresponding thioamides (H) which themselves are commercially availableor can be made from the amide (Phosphorus Sulfur, 1985, 25, 297-305) ornitrile (Chem.-Ztg. 1980, 104, 365; J. Chem. Soc. 1952, 742; Can. J.Chem. 1985, 63, 3075).

[0041] In the cyclization step b of Scheme A, the compound of formula(C) can be reacted with hydrazine or a substituted hydrazine in tolueneat 25 to 110° C. to afford the triazole intermediate (D) in good yieldwith a high degree of regiospecificity. Instead of toluene other aproticsolvents such as tetrahydrofuran (THF) can also be used.

[0042] In step c of Scheme A, the compound of formula (D) can bebrominated with bromine in acetic acid in the presence or absence ofsodium acetate at 25° C. to refluxing temperature to afford the compoundof formula (E).

[0043] In the Suzuki coupling step d of Scheme A, the compound offormula (E) can be reacted with an appropriately substitutedR⁴/R⁵—boronic acid to provide the compound of formula (F). The couplingcan be carried out in an acetonitrile/water mixture or ethanol, at atemperature in the range from ambient to refluxing. Catalytic amounts ofdichlorobis(triphenylphosphine)palladium(II) ortetrakis(triphenylphosphine)palladium(0) are typically used forcoupling, however other Pd(II) or Pd(0) catalysts can also be used.Typically sodium carbonate is used as a base in the reaction, howeverother inorganic bases such as potassium carbonate or organic bases suchas triethylamine can also be used.

[0044] Alternatively, compounds of formula (1) can also be prepared bythe methods illustrated in Scheme B:

[0045] wherein X, Y, R¹, R², R³, R⁴ and R⁵ are defined as in formula(1).

[0046] In step a of Scheme B, the compound of formula (A) is coupledwith the acid chloride of formula (B′) to provide acyl thioimidate offormula (C′) in a similar fashion as described for step a in Scheme A.Acid chlorides of formula (B′) are prepared from correspondingcarboxylic acids of formula (G′)

[0047] which are readily made through known procedures.

[0048] The cyclization step b of Scheme B is performed in a similarfashion as step b of Scheme A to afford the triazole intermediate (E) ingood yield with a high degree of regioselectivity.

[0049] In step c of Scheme B, the Suzuki coupling was performed in asimilar fashion as step d of Scheme A to afford the compound of formula(F).

[0050] Alternatively, compounds of formula (1) can also be prepared bythe methods illustrated in Scheme C:

[0051] wherein X, Y, R¹, R², R³, R⁴ and R⁵ are defined as in formula(1).

[0052] In step a of Scheme C, the compound of formula (A) is coupledwith the acid chloride of formula (B″) to provide acyl thioimidate offormula (C″) in a similar fashion as described for step a in Scheme A.Acid chlorides of formula (B″) are prepared from correspondingcarboxylic acids of formula (G″)

[0053] which are readily made through known procedures.

[0054] The cyclization step b of Scheme C is performed in a similarfashion as step b of Scheme B to afford the triazole (F).

EXAMPLES Example A

[0055] 2,4-Dimethylthiophene-3-carboxylic acid

[0056] n-Butyllithium (2.5 M in hexanes, 18.6 mL, 46 mmol) was added toa pre-cooled solution of 4-methylthiophene-3-carboxylic acid (3.0 g, 21mmol) in dry tetrahydrofuran (THF, 35 mL) at −62° C. The reactionmixture was stirred at −78° C. for an hour, allowed to warm to −40° C.and re-cooled to −78° C. before adding iodomethane (3.28 mL, 7.49 g, 53mmol). After addition, the reactants were stirred at −78° C. for an hourand then allowed to warm to room temperature over 14 hours and quenchedwith water (20 mL). The organic phase was extracted with dilute sodiumhydroxide (0.2 N, 3×30 mL). The combined aqueous extracts were washedwith ether (2×30 mL), cooled in an ice bath and acidified to pH 3 usingconcentrated hydrochloric acid. The resultant precipitate was extractedwith ether (3×50 mL). The combined ethereal extracts were washed withwater (50 mL) and brine (50 mL), dried over magnesium sulphate,concentrated under reduced pressure and recrystallised from ethylacetate/hexane to give product as an amorphous white solid (2.7 g, 82%):mp 164-165° C.; ¹H NMR (CDCl₃) δ 6.65 (q, 1H), 2.73 (s, 3H), 2.43 (d,3H); EI/MS 156 m/e (M⁺); IR (liq film) 1664 cm⁻¹; Calcd for C₇H₈O₂S: C,53.8; H, 5.16; Found: C, 53.8; H, 5.11.

Example B

[0057] 5-Bromo-2,4-dimethylthiophene-3-carboxylic acid

[0058] A solution of bromine (0.73 mL, 2.25 g, 14 mmol) in glacialacetic acid (8 mL) was added to a solution of2,4-dimethylthiophene-3-carboxylic acid (2.1 g, 13 mmol) in glacialacetic acid (24 mL) at 6° C. Upon completion, the reaction was stirredat 10° C. for an hour, diluted with glacial acetic acid (30 mL), stirredfor 14 hours at room temperature, poured into water (400 mL) andextracted with ether (3×40 mL). The combined ethereal extracts wereextracted with dilute sodium hydroxide (0.2 N, 3×30 mL). The combinedbasic extracts were cooled in an ice bath and then acidified to pH 3using concentrated hydrochloric acid. Precipitated solids were extractedwith ether (3×40 mL). Pooled organic extracts were washed with water (50mL) and brine (50 mL), dried over magnesium sulphate and concentratedunder reduced pressure. The residue was recrystallised from ethylacetate/hexane to give product as an amorphous white solid (2.7 g, 85%):mp 183-184° C.; ¹H NMR (CDCl₃) δ 2.67 (s, 3H), 2.38 (s, 3H); EI/MS 235m/e (M⁺); IR (liq film) 1674 cm⁻¹; Calcd. for C₇H₇BrO₂S: C, 35.8; H,3.00; S, 13.6; Found: C, 35.8; H, 2.99; N, 13.5.

Example C

[0059] Ethyl 4,5-dibromo-3-chlorothiophene-2-carboxylate

[0060] Ethyl 3-chlorothiophene-2-carboxylate (3.96 g, 20.7 mol) in asuspension of sodium acetate (12.71 g, 154 mmol) and glacial acetic acid(35 mL) was treated with bromine (9.6 mL, 186.3 mmol). The reactionmixture was stirred at 75° C. under N₂ for 136 hours and then at 25° C.for 144 hours. The reaction mixture was poured onto ice cold satd aqsodium bicarbonate and aq sodium metabisulfite. The mixture was stirredwith ether (100 mL) for 30 minutes. Extraction with ether (3×150 mL)gave an organic layer that was washed with water (150 mL) and satd aqsodium chloride (150 mL), dried over magnesium sulfate and concentratedto give product as a white solid (5.83 g, 80%): mp 58-63° C.; ¹H NMR(CDCl₃) δ 4.37 (q, 2H, J=7.1 Hz), 1.38 (t, 3H, J=7.1 Hz,); EI/MS 347 m/e(M⁺).

Example D

[0061] 4,5-Dibromo-3-chlorothiophene-2-carboxylic acid

[0062] Ethyl 4,5-dibromo-3-chlorothiophene-2-carboxylate (5.52 g, 15.8mmol) and lithium hydroxide (0.716 g, 31.7 mmol) were taken up inmixture of THF (30 mL) and water (30 mL). The reaction mixture wasstirred at 25° C. for 32 hours. The aqueous layer was made acidic by thedropwise addition of conc hydrochloric acid and extracted with ether(3×50 mL). The combined organic extracts were dried over sodium sulfate,filtered and concentrated to give the product as a white solid (4.38 g,86%) that was used without purification: mp 209-223° C. (d); ¹H NMR(CDCl₃ and DMSO-d₆) δ 4.15 (bs, 1H); EI/MS 320 m/e (M⁺).

Example E

[0063] Methyl2-chloro-6-fluoro-N-[(4-methylthien-3-yl)carbonyl]benzenecarbimidothioate

[0064] To a suspension of 4-methylthiophene-3-carboxylic acid (2.74 g,19 mmol) in 1,2-dichloroethane (DCE, 100 mL) was added thionyl chloride(5.67 mL, 9.25 g, 78 mmol) and dimethylformamide (DMF, 10 drops from aPasteur pipette). After refluxing under nitrogen for 4 hours, thereaction mixture was concentrated under reduced pressure. The residuewas taken up in DCE (80 mL) and concentrated once again under reducedpressure. This residue was dissolved in DCE (30 mL) and added at adropwise rate into a suspension ofS-methylthio-2-chloro-6-fluorobenzamidinium bromide (5.5 g, 19 mmol) inDCE (50 mL) at −3° C. Upon completion, a solution of dry pyridine (4.72mL, 4.61 g, 58 mmol) in DCE (3 mL) was added at a rate required tomaintain the temperature below 0° C. The reaction was allowed to come toroom temperature over 14 hours, washed with water (100 mL), saturatedaqueous sodium carbonate (100 mL) and brine (70 mL), dried overmagnesium sulphate and concentrated under reduced pressure to leave athick, yellow liquid which solidified upon standing at room temperaturefor several hours (4.33 g, 68%): ¹H NMR (CDCl₃) δ 8.09 (d, 1H),7.27-7.32 (m, 1H), 7.16 (d, 1H), 7.00 (t, 1H), 6.87 (d, 1H), 2.58 (s,3H), 2.34 (s, 3H); EI/MS: 327 m/e (M-1); IR (liq film) 1669, 1612 and1599 cm⁻¹.

[0065] The following compounds were prepared according to the generalprocedure of Example E.

[0066] Methyl2-chloro-N-[(4,5-dibromo-3-chlorothien-2-yl)carbonyl]-6-fluorobenzenecarbimidothioate

[0067] Product was isolated as a burnt orange solid (73% yield): mp111-118° C.; ¹H NMR (CDCl₃) δ 7.32 (ddd, 1H, J=5.8, 8.0, 8.4 Hz), 7.19(d, 1H, J=8.0 Hz), 7.03 (ddd, 1H, J=0.85, 8.0, 8.4 Hz) 2.65 (s, 3H);EI/MS 470 m/e (M-Cl).

[0068] Methyl2-chloro-N-[(4-chlorothien-3-yl)carbonyl]-6-fluorobenzenecarbimidothioate

[0069] Product was isolated as a dark brown liquid that turned to a waxysolid over time (85% yield): ¹H NMR (CDCl₃) δ 8.12 (d, 1H, J=3.6 Hz),7.33-7.25 (m, 2H), 7.18 (dd, 1H, J=1.09, 0.73 Hz), 7.14 (d, 1H, J=3.6Hz), 7.03 (dd, 1H, J=1.09, 8.4 Hz), 2.60 (s, 3H); EI/MS 348 m/e (M⁺).

Example F

[0070]3-(2-Chloro-6-fluorophenyl)-1-methyl-5-(4-methylthien-3-yl)-1H-1,2,4-triazole

[0071] A solution of methylhydrazine (2.02 mL, 1.75 g, 38 mmol) intoluene (5 mL) was added at a rapid dropwise rate to a solution ofmethyl2-chloro-6-fluoro-N-[(4-methylthien-3-yl)carbonyl]benzenecarbimidothioate(4.15 g, 12.7 mmol) in dry toluene (100 mL) at 55° C. The reaction wasstirred at this temperature for 10 minutes and then left at roomtemperature for 14 hours. Another identical portion of methylhydrazinein toluene was added at room temperature and the reaction was heated at80° C. for 3 hours and refluxed for an additional 3 hours. After coolingto room temperature, the reaction mixture was washed with water (100mL), dilute hydrochloric acid (0.05 N, 2×100 mL) and brine (70 mL),dried over magnesium sulphate and concentrated under reduced pressure.The residue was recrystallised from ethyl acetate/hexane to give whitecubes. The mother liquor was chromatographed (eluant, 30:9:1hexane/methylene chloride/acetonitrile to afford the product (3.25 g,84%): mp 153-155° C.; ¹H NMR (CDCl₃) δ 7.54 (d, 1H), 7.26-7.38 (m, 2H),7.06-7.13 (m, 2H), 3.98 (s, 3H), 2.35 (d, 3H); “⁹F NMR (externalreference)-110 ppm; EI/MS 307 m/e (M−1).

[0072] The following compounds were prepared according to the generalprocedure of Example F.

[0073]3-(2-Chloro-6-fluorophenyl)-5-(4,5-dibromo-3-chlorothien-2-yl)-1-methyl-1H-1,2,4-triazole

[0074] Product was isolated as a tan solid (24% yield): mp 180-182° C.;¹H NMR (CDCl₃) δ 7.40-7.27 (m, 2H), 7.14-7.08 (m, 1H), 4.03 (s, 3H);EI/MS 485 m/e (M⁺).

[0075]3-(2-Chloro-6-fluorophenyl)-5-(4-chlorothien-3-yl)-1-methyl-1H-1,2,4-triazole

[0076] Product was isolated as a tan solid (28% yield): mp 126-133° C.;¹H NMR (CDCl₃) δ 7.72 (d, 1H, J=3.6 Hz), 7.39-7.28 (m, 3H), 7.13-7.07(m, 1H), 3.96 (s, 3H); EI/MS 327 m/e (M⁺); Calcd for C₁₃H₈Cl₂FN₃S: C,47.58; H, 2.46; N, 12.80; S, 9.77; Found: C, 47.45; H, 2.40; N, 12.56;S, 9.51.

Example G

[0077]3-(2-Chloro-6-fluorophenyl)-(5-bromo-4-methylthien-3-yl)-1-methyl-1H-1,2,4-triazole

[0078] A suspension of3-(2-chloro-6-fluorophenyl)-1-methyl-5-(4-methylthien-3-yl)-1H-1,2,4-triazole(2.35 g, 7.6 mmol) in glacial acetic acid (15 mL) was heated to 45° C.in order to effect solubilization. After cooling to 10° C., a solutionof bromine (1.34 g, 0.43 mL, 8.4 mmol) in glacial acetic acid (4 mL) wasadded and the thick gel formed was stirred for 14 hours at roomtemperature. The reaction mixture was poured into cold water (100 mL)and extracted with ether (3×70 mL). The combined ethereal extracts werewashed with water (100 mL), saturated aqueous sodium bicarbonate (2×100mL), aqueous sodium bisulphite (10% solution, 300 mL) and brine (100mL), dried over magnesium sulphate and concentrated under reducedpressure. Recrystallisation from ethyl acetate/hexane afforded yellowcubes. The mother liquor was chromatographed over silica gel to affordthe product as colorless cubes (2.6 g, 89%): mp 133-134° C.; ¹H NMR(CDCl₃) δ 7.51 (s, 1H), 7.29-7.39 (m, 2H), 7.11 (t, 1H), 3.98 (s, 3H),2.27 (s, 3H); EI/MS 386 m/e (M⁺).

[0079] The following compounds were prepared according to the generalprocedure of Example G.

[0080]3-(2,6-Difluorophenyl)-5-(5-bromo-3-chlorothien-2-yl)-1-methyl-1H-1,2,4-triazole

[0081] Product was isolated as a white solid (51% yield): mp 134-137°C.; ¹H NMR (CDCl₃) δ 7.43-7.33 (m, 1H), 7.08 (s, 1H), 7.06-6.98 (m, 2H),4.02 (s, 3H); EI/MS 391 m/e (M+H); Calcd for C₁₃H₇BrClF₂N₃S: C, 39.97;H, 1.81; N, 10.76; S, 8.21; Found: C, 39.74; H, 1.82; N, 10.54; S, 8.27.

[0082]3-(2-Chloro-6-fluorophenyl)-5-(5-bromo-4-chlorothien-3-yl)-1-methyl-1H-1,2,4-triazole

[0083] Product was isolated as a light yellow solid (51% yield): mp111-117° C.; ¹H NMR (CDCl₃) δ 7.71 (s, 1H), 7.39-7.29 (m, 2H), 7.14-7.08(m, 1H), 3.97 (s, 3H); EI/MS 407 m/e (M⁺); Calcd for C₁₃H₇BrCl₂FN₃S: C,38.36; H, 1.73; N, 10.32; Found: C, 38.57; H, 1.71; N, 10.18.

Example H

[0084]3-(2-Chloro-6-fluorophenyl)-5-(4-bromo-3,5-dimethylthien-2-yl)-1-methyl-1H-1,2,4-triazole

[0085] n-Butyllithium (0.7 g, 10.8 mmol) was added dropwise to asolution of5-(4,5-dibromo-3-methylthien-2-yl)-3-(2-chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazole(5 g, 10.8 mmol) in THF (70 mL) at −70° C. and stirred for 1 hour.Iodomethane (1.6 g, 11.29 mmol) was added to the reaction mixture andallowed to warm to 25° C. After adding saturated aq ammonium chloride(10 mL), the organic layer was separated, washed with water, followed bysaturated aq sodium chloride (20 mL) and dried over sodium sulfate,filtered, and concentrated. The residue was chromatographed to give theproduct as a yellow oil (2.0 g, 47%): ¹H NMR (CDCl₃) δ 2.32 (s, 3H),2.48 (s, 3H), 3.99 (s, 3H), 7.07-7.13 (m, 1H), 7.28-7.38 (m, 2H); EI/MS400 m/e (M⁺); Calcd. for C₁₅H₁₂ClBrFN₃S: C, 44.96; H, 3.02; N, 10.49;Found: C, 44.94; H, 3.01; N, 10.29.

Example 0

[0086] 2-Fluoro-4-trifluoromethoxybenzeneboronic acid

[0087] To a solution of n-butyllithium (2.5 M solution in hexanes, 14.1mL) in THF (30 mL) at −98° C. was added a solution of4-bromo-3-fluorotrifluoromethoxy-benzene in THF (3 mL). After stirringfor 10 min. at −98° C., triisopropyl borate (4.88 mL, 3.98 g, 21 mmol)was added at a rate needed to keep the temperature below −97° C. Thereaction mixture was allowed to warm to −30° C. over 30 minutes,re-cooled to −78° C. and stirred at this temperature for 30 min.Concentrated hydrochloric acid (2 mL) was added and the reaction mixturewas concentrated under reduced pressure. Dilute hydrochloric acid (0.2N, 15 mL) was added and the mixture was extracted with ether (3×20 mL).The combined ethereal layers were extracted with dilute sodium hydroxide(0.02 N, 3×30 mL). The combined aqueous extracts were cooled to 0° C.,acidified to pH 3.5 using concentrated hydrochloric acid and extractedwith ether (3×30 mL). The combined ethereal layers were then washed withwater (15 mL) and brine (15 mL), dried over magnesium sulphate andconcentrated under reduced pressure to leave 2.3 g of yellow solid.Recrystallisation from hexane afforded pink needles (1.25 g, 41%): mp89-93° C.; ¹H NMR (CDCl₃) δ 7.89 (t, 1H), 7.07 (d, 1H), 6.94 (d, 1H),5.11 (d, 2H); EI/MS 223 m/e (M−1).

[0088] The following compounds were prepared according to the generalprocedure of Example I.

[0089] 2-Fluoro-4-trifluoromethylbenzeneboronic acid

[0090] Product was isolated as a yellow solid (30% yield): mp 115-116°C.; ¹H NMR (CDCl₃) δ 7.98 (t, 1H), 7.47 (d, 1H), 7.32 (d, 1H), 5.11 (d,1H); EI/MS 207 m/e (M−1); IR (liq film) 1331 cm⁻¹.

[0091] 2-Fluoro-5-trifluoromethylbenzeneboronic acid

[0092] Product was isolated as iridescent plates (24% yield): ¹H NMR(CDCl₃) δ 7.61 (m, 1H), 7.51 (m, 1H), 7.04 (m, 1H), 5.11 (d, 1H); EI/MS207 m/e (M−1); IR (liq film) 1361 cm⁻¹; Calcd. for C₇H₅BF₄O₂: C, 40.44;H, 2.42; Found: C, 39.79; H, 2.33.

Example J

[0093]4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,1,2,2-tetrafluoroethoxybenzene

[0094] Triethylamine (4.59 mL, 3.33 g, 33 mmol) and4-(1,1,2,2-tetrafluoroethoxy)-bromobenzene (3 g, 11 mmol) were added toa suspension of 1,1′-bis-[diphenylphosphino]ferrocenedichloropalladium(II) in dry dioxane (45 mL). Neat 4,4,5,5-tetramethyl-1,3,2-dioxaborane(2.39 mL, 2.11 g, 16 mmol) was then added to this mixture and refluxedfor three days. After cooling to room temperature, the reaction mixturewas poured into water (300 mL) and extracted with ether (3×100 mL). Thecombined ethereal extracts were washed with water (150 mL) and brine (70mL), dried over magnesium sulphate, concentrated under reduced pressureand distilled at 0.06 mm Hg (99° C.) to afford the product (1.88 g, 53%)as a yellow oil: ¹H NMR (CDCl₃) δ 7.83 (d, 2H), 7.20 (d, 2H), 6.08, 5.90& 5.72 (tt, 1H), 1.34 (s, 12H); EI/MS 320 m/e (M⁺); IR (liq film) 1364cm⁻¹.

Example 1

[0095]3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0096] A mixture of 4-trifluoromethoxybenzeneboronic acid (0.4 g, 1.1mmol),3-(2-chloro-6-fluorophenyl)-5-[5-bromo-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole(0.4 g, 1 mmol), sodium carbonate (0.2 g, 1.9 mmol),tri-o-tolylphosphine (32 mg, 0.1 mmol) anddichlorobis(triphenylphosphine)palladium(II) (73 mg, 0.1 mmol) wererefluxed under nitrogen for 16 hours in an acetonitrile (14 mL) andwater (1.4 mL) solution. After cooling to room temperature, thereactants were poured into dilute hydrochloric acid (1 N, 50 mL) andextracted with ether (3×50 mL). The combined ethereal extracts werewashed with water (100 mL), saturated aqueous bicarbonate (70 mL) andbrine (50 mL), dried over magnesium sulphate, filtered and concentrated.The residue was chromatographed over silica to afford the product as ayellow gum (210 mg, 43%): ¹H NMR (CDCl₃) δ 7.55 (s, 1H), 7.49 (d, 2H),7.28-7.39 (m, 4H), 7.11 (t, 1H), 4.03 (s, 3H), 2.33 (s,3H); EI/MS 467m/e (M−1).

[0097] The following compounds were prepared according to the generalprocedure of Example 1.

[0098]3-(2-Chloro-6-fluorophenyl)-5-{4-chloro-5-[4-(trifluoromethoxy)phenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

[0099] Product was isolated as a white solid: mp 112-116° C.; ¹H NMR(CDCl₃) δ 7.72 (t, 3H, J=4.3 Hz), 7.40-7.30 (m, 4H), 7.15-7.09 (m, 1H),4.09 (s, 3H); EI/MS 487 m/e (M⁺); Calcd for C₂₀H₁₁Cl₂F₄N₃OS: C, 49.20;H, 2.27; N, 8.61; Found: C, 48.95; H, 2.24; N, 8.48.

[0100]3-(2-Chloro-6-fluorophenyl)-5-{4-chloro-5-[4-(trifluoromethyl)phenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

[0101] Product was isolated as a white solid (66% yield): mp 88-92° C.;¹H NMR (CDCl₃) δ 7.82 (d, 2H, J=8.0 Hz), 7.76 (s, 1H), 7.74 (d, 2H,J=8.0 Hz), 7.40-7.30 (m, 2H), 7.15-7.09 (m, 1H), 6.96-6.92 (m, 1H), 4.02(m, 3H); EI/MS 471 m/e (M⁺); Calcd for C₂₀H₁₁Cl₂F₄N₃S: C, 50.86; H,2.35; N, 8.90; Found: C, 50.81; H, 2.39; N, 8.77.

[0102]3-(2-Chloro-6-fluorophenyl)-5-[4-chloro-5-(4-ethoxyohenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0103] Product was isolated as a light yellow solid (77% yield): mp120-128° C.; ¹H NMR (CDCl₃) δ 7.63-7.58 (m, 3H), 7.39-7.29 (m, 2H),7.14-7.08 (m, 1H), 7.01-6.96 (m, 2H), 4.09 (q, 2H, J=6.9 Hz), 4.00 (s,3H), 1.45 (t, 3H, J=6.9 Hz); EI/MS 447 m/e (M⁺).

[0104]3-(2,6-Difluorophenyl)-5-[5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0105] Product was isolated as a yellowish solid (37% yield): mp 88-91°C.; ¹H NMR (CDCl₃) δ 7.75 (d, 1H), 7.72 (d, 1H), 7.67 (d, 2H), 7.36-7.43(m, 1H), 7.02 (t, 1H), 4.17 (s, 3H); EI/MS 437 m/e (M⁺).

[0106]3-(2-Chloro-6-fluorophenyl)-5-[5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0107] Product was isolated as a yellow solid (88% yield): mp 124-125°C.; ¹H NMR (CDCl₃) δ 7.77 (d, 1H), 7.74 (d, 1H), 7.67 (d, 2H), 7.25-7.40(m, 4H), 7.11 (t, 1H), 4.19 (s, 3H); EI/MS: 453 m/e (M−1); Calcd. forC₂₀H₁₂ClF₄N₃OS: C, 52.9; H, 2.67; N, 9.26; S, 7.06; Found: C, 53.1; H,2.67; N, 8.7; S, 7.0.

[0108]3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0109] Product was isolated as an amorphous white solid (32% yield): mp121° C.; ¹H NMR (CDCl₃) δ 8.02 (s, 11H), 7.89 (s, 11H), 7.82 (t, 11H),7.47 (s, 11H), 7.43 (d,1H), 7.29-7.39 (m, 2H), 7.11 (t, 11H), 4.19 (s,31H); EI/MS: 471 m/e (M−1); Calcd. for C₂₁H₁₅ClF₅N₃S: C, 53.5; H, 3.20;N, 8.90; Found: C, 53.3; H, 2.91; N, 8.91.

[0110]3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-4-methylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0111] Product was isolated as yellow prisms (32% yield): mp 128-129°C.; ¹H NMR (CDCl₃) δ 7.86 (d, 1H), 7.79 (d, 1H), 7.55 (t, 1H), 7.28-7.39(m, 2H), 7.11 (t, 1H), 4.17 (s, 3H), 2.38 (s, 3H); EI/MS 402 m/e (M⁺);Calcd. for C₂₀H₁₄ClF₂N₃S: C, 59.8; H, 3.51; N, 10.5; Found: C, 59.6; H,3.44; N, 10.3.

[0112]3-(2-Chloro-6-fluorophenyl)-5-[5-(3-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0113] Product was isolated as a yellow gum (66% yield): ¹H NMR (CDCl₃)δ 7.82 (d, 1H), 7.88 (d, 2H), 7.82 (d, 2H), 7.78 (d, 1H), 7.53-7.58 (m,2H), 7.34-7.38 (m, 2H), 7.11 (t, 1H), 4.20 (s, 3H); EI/MS 437 m/e (M−1);Calcd. for C₂₀H₁₂ClF₄N₃S: C, 54.9; H, 2.76; N, 9.60; Found: C, 55.2; H,2.94; N, 9.60.

[0114]3-(2-Chloro-6-fluorophenyl)-5-[5-(4-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0115] Product was isolated as a yellow solid (80% yield): mp 166° C.;¹H NMR (CDCl₃) δ 7.88 (d, 1H), 7.78 (d, 1H), 7.75 (d, 2H), 7.66 (d, 2H),7.29-7.40 (m, 2H), 7.11 (t, 1H), 4.19 (s, 3H); EI/MS 437 m/e (M−1).

[0116]3-(2-Chloro-6-fluorophenyl)-5-[5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0117] Product was isolated as yellowish crystals (56% yield): mp113-114° C.; ¹H NMR (CDCl₃) δ 7.66 (d, 1H), 7.65 (d, 1H), 7.56 (d, 2H),7.29-7.39 (m, 2H), 7.10 (t, 1H), 4.17 (s, 3H), 4.07 (q, 2H), 1.44 (t,3H); EI/MS 413 m/e (M−1); Calcd. for C₂₁H₁₇ClFN₃SO: C, 60.9; H, 4.14; N,10.2; S, 7.75; Found: C, 60.7; H, 4.16; N, 9.93; S, 7.61.

[0118]3-(2,6-Difluorophenyl)-5-[5-(4-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0119] Product was isolated as a yellow solid (37% yield): mp 143-146°C.; ¹H NMR (CDCl₃) δ 7.88 (d, 1H), 7.77 (d, 1H), 7.75 (d, 2H), 7.66 (d,2H), 7.33-7.43 (m, 1H), 7.05 (t, 1H), 4.17 (s, 3H); EI/MS 421 m/e (M⁺).

[0120]3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(2,3-dihydro-1-benzofuran-5-yl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0121] Product was isolated as a yellowish amorphous solid (21% yield):mp 180° C.; ¹H NMR (CDCl₃) δ 7.29-7.40 (m, 2H), 7.26 (s, 1H), 7.10-7.14(m, 2H), 6.89 (d, 1H), 4.04 (s, 3H), 3.93 (s, 3H), 3.92 (s, 3H); EI/MS446 m/e (M⁺); Calcd. for C₂₁H₁₆Cl₂FN₃OS: C, 54.3; H, 3.47; N, 9.05;Found: C, 54.1; H, 3.52; N, 8.76.

[0122]3-(2-Chloro-6-fluorolphenyl)-5-[2-chloro-5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0123] Product was isolated as a white solid (10% yield): mp 172° C.; ¹HNMR (CDCl₃) δ 7.45 (d, 2H), 7.29-7.39 (m, 2H), 7.23 (s, 1H), 7.11 (m,1H), 6.91 (d, 1H), 4.06 (q, 2H), 4.03 (s, 3H), 1.44 (t, 3H); EI/MS 448m/e (M⁺).

[0124]3-(2-Chloro-6-fluorophenyl)-5-[2-methyl-5-(4-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0125] Product was isolated as white cubes (62% yield): mp 167-168° C.;¹H NMR (CDCl₃) δ 7.67 (d, 2H), 7.65 (d, 2H), 7.42 (s, 1H), 7.29-7.39 (m,2H), 7.11 (m, 1H), 4.01 (s, 3H), 2.64 (s, 3H); EI/MS 452 m/e (M⁺);Calcd. for C₂₁H₁₄ClF₄N₃S: C, 55.8; H, 3.12; N, 9.30; Found: C, 55.9; H,3.27; N, 9.32.

[0126]3-(2-Chloro-6-fluorophenyl)-5-[2-methyl-5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0127] Product was isolated as white needles (75% yield): mp 184-185°C.; ¹H NMR (CDCl₃) δ 7.48 (d, 2H), 7.28-7.38 (m, 2H), 7.20 (s, 1H), 7.20(s, 1H), 7.10 (m, 1H), 6.91 (d, 2H), 4.06 (q, 2H), 4.00 (s, 3H), 2.60(s, 3H), 1.44 (t, 3H); EI/MS 428 m/e (M⁺); Calcd. for C₂₁H₁₄ClF₄N₃S: C,55.8; H, 3.12; N, 9.30; Found: C, 55.9; H, 3.27; N, 9.32.

[0128]3-(2-Chloro-6-fluorophenyl)-5-[2-methyl-5-(3-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0129] Product was isolated as iridescent flakes (52% yield): mp124-125° C.; ¹H NMR (CDCl₃) δ 7.29-7.52 (m, 6H), 7.08-7.18 (m, 2H);EI/MS 468 m/e (M⁺); Calcd. for C₂₁H₁₄ClF₄N₃OS: C, 53.9; H, 3.02; N,8.98; Found: C, 53.8; H, 2.90; N, 8.87.

[0130]3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-4-methylphenyl)-2-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0131] Product was isolated as iridescent plates (17% yield): mp168-169° C.; ¹H NMR (CDCl₃) δ 7.44-7.49 (m, 2H), 7.29-7.38 (m, 2H), 7.10(m, 1H), 6.97 (s, 1H), 6.96 (d, 1H), 4.01 (s, 3H), 2.64 (s, 3H), 2.37(s, 3H); EI/MS 416 m/e (M⁺).

[0132]3-(2-Chloro-6-fluorophenyl)-5-[5-(3,4-dichlorophenyl)-2-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0133] Product was isolated as an amorphous white solid (28% yield): mp162-163° C.; ¹H NMR (CDCl₃) δ 7.65 (d, 1H), 7.45 (d, 11H), 7.29-7.40 (m,4H), 7.11 (m, 1H), 4.01 (s, 3H), 2.62 (s, 3H); EI/MS 454 m/e (M+1);Calcd. for C₂₀H₁₃Cl₂FN₃S: C, 53.1; H, 2.81; N, 9.28; Found: C, 53.1; H,2.93; N, 9.12.

[0134]3-(2-Chloro-6-fluorophenyl)-5-[5-(4-chloro-2-fluorophenyl)-2-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0135] Product was isolated as iridescent plates (39% yield): mp177-178° C.; ¹H NMR (CDCl₃) δ 7.60 (dd, 1H), 7.40-7.45 (m, 1H),7.27-7.38 (m, 3H), 7.08-7.20 (m, 2H), 4.01 (s, 3H), 2.62 (s, 3H); EI/MS436 m/e (M⁺); Calcd. for C₂₀H₁₃Cl₂F₂N₃S: C, 55.1; H, 3.00; N, 9.63;Found: C, 54.8; H, 3.07; N, 9.46.

[0136]3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-4-trifluoromethylphenyl)-2-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0137] Product was isolated as colorless needles (14% yield): mp153-154° C.; ¹H NMR (CDCl₃) δ 7.71 (t, 1H), 7.61 (s, 1H), 7.42-7.46 (m,H), 7.29-7.39 (m, 2H), 7.11 (m, 1H), 4.02 (s, 3H), 2.66 (s, 3H); EI/MS470 m/e (M⁺).

[0138]3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-5-trifluoromethylphenyl)-2-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0139] Product was isolated as a white solid (27% yield): mp 141-142°C.; ¹H NMR (CDCl₃) δ 7.86 (dd, 1H), 7.58 (s, 1H), 7.56 (m, 1H),7.28-7.39 (m, 3H), 7.11 (m,1H), 4.02 (s, 3H), 2.66 (s, 3H); EI/MS 470m/e (M+2); Calcd. for C₂₁H₁₃ClF₅N₃S: C, 53.7; H, 2.79; N, 8.94; Found:C, 53.5; H, 2.85; N, 8.94.

[0140]3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0141] Product was isolated as an amorphous, white solid (14% yield): mp153-155° C.; ¹H NMR (CDCl₃) δ 7.44 (d, 2H), 7.29-7.39 (m, 2H), 7.22 (s,1H), 7.11 (t, 1H), 6.90 (d, 2H), 4.03-4.09 (m, 5H), 1.43 (t, 3H); EI/MS450 m/e (M+2); Calcd. for C₂₂H₁₉ClFN₃OS: C, 61.8; H, 4.48; N, 9.82;Found: C, 61.4; H, 4.42; N, 9.71.

[0142]3-(2-Chloro-6-fluorophenyl-5-[4-methyl-5-(4-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0143] Product was isolated as a yellow gum (38% yield): ¹H NMR (CDCl₃)δ 7.71 (d, 2H), 7.60 (d, 2H), 7.59 (s, 1H), 7.30-7.40 (m, 2H), 7.11 (t,1H), 4.04 (s, 3H), 2.36 (s, 3H); EI/MS 451 m/e (M−1).3-(2-Chloro-6-fluorophenyl)-5-[5-(4-chlorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0144] Product was isolated as a sticky, yellow foam (30% yield): ¹H NMR(CDCl₃) δ 7.54 (s, 1H), 7.38-7.41 (m, 4H), 7.29-7.35 (m, 2H), 7.11 (t,1H), 4.03 (s, 3H), 2.32 (s, 3H); EI/MS 417 m/e (M−1).

[0145]3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0146] Product was isolated as white needles (50% yield): mp 131-132°C.; ¹H NMR (CDCl₃) δ 7.47 (s, 1H), 7.38 (d, 4H), 7.29 7.36 (m, 2H), 7.11(t, 1H), 6.96 (d, 2H), 4.08 (q, 2H), 4.02 (s, 3H), 2.30 (s, 3H), 1.45(t, 3H); EI/MS 427 m/e (M−1).

[0147]3-(2-Chloro-6-fluorophenyl)-5-[5-(4-methoxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0148] Product was isolated as a yellow glass (30% yield): ¹H NMR(CDCl₃) δ 7.48 (s, 1H), 7.41 (d, 2H), 7.29-7.38 (m, 2H), 7.11 (t, 1H),6.98 (d, 2H), 4.03 (s, 3H), 3.85 (s, 3H), 2.31 (s, 3H); EI/MS 413 m/e(M−1).

[0149]3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(4-methylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0150] Product was isolated as an off-white solid (39% yield): mp158-159° C.; ¹H NMR (CDCl₃) δ 7.50 (s, 1H), 7.29-7.39 (m, 4H), 7.27 (d,2H), 7.11 (t, 1H), 4.03 (s, 3H), 2.32 (s,3H); EI/MS 397 m/e (M−1).

[0151]3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(3-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0152] Product was isolated as a yellowish solid (16% yield): mp 133°C.; ¹H NMR (CDCl₃) δ 7.57 (s, 1H), 7.30-7.51 (m, 6H), 7.11 (t, 1H), 4.04(s, 3H), 2.34 (s,3H); EI/MS 467 m/e (M−1).

[0153]3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(3-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0154] Product was isolated as free-flowing cubes (48% yield): mp134-135° C.; ¹H NMR (CDCl₃) δ 7.73 (br s, 1H), 7.55-7.67 (m, 4H),7.29-7.39 (m, 2H), 7.11 (t, 1H), 4.04 (s, 3H), 2.34 (s, 3H); EI/MS 451m/e (M−1); Calcd. for C₂₁H₁₄ClF₄N₃S: C, 55.9; H, 3.13; N, 9.31; S, 7.09;Found: C, 55.8; H, 3.26; N, 9.26; S, 7.16.

[0155]3-(2-Chloro-6-fluorophenyl)-5-[5-(3-ethoxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0156] Product was isolated as a yellow solid (65% yield): mp 98-99° C.;¹H NMR (CDCl₃) δ 7.51 (s, 1H), 7.26-7.39 (m, 3H), 7.00-7.14 (m, 2H),6.92 (dd, 1H), 4.07 (q, 2H), 4.02 (s, 3H), 2.34 (s, 3H), 1.43 (t, 3H);EI/MS 427 m/e (M−1).

[0157]3-(2-Chloro-6-fluorophenyl-5-[4-methyl-5-(4-methylthiophenyl)thien-3-yl]-1-methyl-1H-1,24-triazole

[0158] Product was isolated as a white, fluffy solid (74% yield): mp163-164° C.; ¹H NMR (CDCl₃) δ 7.51 (s, 1H), 7.40 (d, 2H), 7.29-7.37 (m,4H), 7.11 (t, 1H), 4.03 (s, 3H), 2.53 (s, 3H), 2.32 (s, 3H); EI/MS 429m/e (M−1).

[0159]3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(4-phenoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0160] Product was isolated as a yellow foam (51% yield): ¹H NMR (CDCl₃)δ 7.50 (s, 1H), 7.29-7.45 (m, 6H), 7.04-7.17 (m, 6H), 4.03 (s, 3H), 2.33(s, 3H); EI/MS 475 m/e (M−1).

[0161]3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(4-isopropyl)phenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0162] Product was isolated as needles (15% yield): mp 143-144° C.; ¹HNMR (CDCl₃) δ 7.49 (s, 1H), 7.41 (d, 2H), 7.29-7.37 (m, 4H), 7.11 (m,1H), 4.03 (s, 3H), 2.96 (pentet, 1H), 2.33 (s, 3H), 1.29 (d, 6H); EI/MS426 m/e (M⁺).

[0163]3-(2-Chloro-6-fluorophenyl)-5-{5-[(3-fluorophenyl)-4-methyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

[0164] Product was isolated as an amorphous white solid (89% yield): mp143-144° C.;

[0165]¹H NMR (CDCl₃) δ 7.55 (s, 1H), 7.04-7.44 (m, 7H), 4.02 (s, 3H),2.35 (s, 3H); EI/MS 402 m/e (M⁺); Calcd. for C₂₀H₁₄ClF₂N₃S: C, 59.8; H,3.5; N, 10.5; Found: C, 59.8; H, 3.56; N, 10.3.

[0166]3-(2-Chloro-6-fluorophenyl)-5-{4-methyl-5-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

[0167] Product was isolated as a white solid (72% yield): mp 185-186°C.; ¹H NMR (CDCl₃) δ 7.49 (s, 1H), 7.44 (d, 2H), 7.29-7.38 (m, 2H),7.09-7.18 (m, 3H), 5.49 (m, 1H), 3.88-3.97 (m, 1H), 4.03 (s, 3H),3.62-3.68 (m, 1H), 2.35 (s, 3H), 1.98-2.07 (m, 1H), 1.87-1.91 (m, 2H),1.60-1.73 (m, 3H); EI/MS 484 m/e (M⁺); Calcd. for C₂₀H₁₄ClF₂N₃S: C,59.8; H, 3.5; N, 10.5; Found: C, 59.8; H, 3.56; N, 10.3.

[0168]3-(2-Chloro-6-fluorophenyl)-5-[5-(3,4-difluorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0169] Product was isolated as white cubes (28% yield): mp 93° C.; ¹HNMR (CDCl₃) δ 7.54 (s, 1H), 7.28-7.37 (m, 3H), 7.19-7.25 (m, 2H), 7.11(t, 1H), 4.03 (s, 3H), 2.32 (s, 3H); EI/MS 419 (M−1).

[0170]3-(2-Chloro-6-fluorophenyl)-5-[5-(3-chloro-4-methylphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0171] Product was isolated as white micro-needles (53% yield): mp136-137° C.; ¹H NMR (CDCl₃) δ 7.53 (s, 1H), 7.46 (s, 1H), 7.27-7.37 (m,4H), 7.11 (t, 1H), 4.02 (s, 3H), 2.42 (s, 3H), 2.32 (s, 3H); EI/MS 432m/e (M⁺); Calcd. for C₂₁H₁₆Cl₂FN₃S: C, 58.3; H, 3.73; N, 9.7; S, 7.4;Found: C, 58.0; H, 3.72; N, 9.43; S, 7.22.

[0172]3-(2-Chloro-6-fluorophenyl)-5-[5-(3-chloro-2-trifluoromethylphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0173] Product was isolated as a yellowish foam (15% yield): ¹H NMR(CDCl₃) δ 7.78 (d, 1H), 7.65 (s, 1H), 7.58 (d, 1H), 7.45 (s, 1H),7.29-7.39 (m, 2H), 7.11 (t, 1H), 4.05 (s, 3H), 2.14 (s, 3H); EI/MS 485m/e (M−1).

[0174]3-(2-Chloro-6-fluorophenyl)-5-[5-(4-chloro-3-trifluoromethylphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0175] Product was isolated as a colourless glass (8% yield): ¹H NMR(CDCl₃) δ 7.79 (s, 1H), 7.58 (m, 1H), 7.29-7.39 (m, 2H), 7.11 (t, 1H),4.03 (s, 3H), 2.33 (s, 3H); EI/MS 485 m/e (M−1).

[0176]3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-4-trifluoromethylphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0177] Product was isolated as a yellow glass (39% yield): ¹H NMR(CDCl₃) δ 7.68 (s, 1H), 7.46-7.54 (m, 3H), 7.29-7.39 (m, 2H), 7.11 (m,1H), 4.04 (s, 3H), 2.25 (s, 3H); EI/MS 470 (M⁺).

[0178]3-(2-Chloro-6-fluorophenyl)-5-[5-(2-chloro-4-trifluoromethylphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0179] Product was isolated as an amorphous, yellowish solid (66%yield): mp 65-66° C.;

[0180]¹H NMR (CDCl₃) δ 7.78 (s, 1H), 7.66 (s, 1H), 7.60 (d, 1H), 7.52(d, 1H), 7.29-7.39 (m, 2H), 7.11 (m, 1H), 4.05 (s, 3H), 2.17 (s, 3H);EI/MS 486 m/e (M⁺); Calcd. for C₂₁H₁₃Cl₂F₄N₃S: C, 51.9; H, 2.69; N,8.64; Found: C, 51.6; H, 2.82; N, 8.45.

[0181]3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-4-trifluoromethoxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0182] Product was isolated as a colorless gum (33% yield): ¹H NMR(CDCl₃) δ 7.64 (s, 1H), 7.29-7.46 (m, 3H), 7.08-7.14 (m, 3H), 4.04 (s,3H), 2.23 (d, 3H); EI/MS 485 m/e (M−1).

[0183]3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-5-trifluoromethylphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0184] Product was isolated as a colorless glass (11% yield): ¹H NMR(CDCl₃) δ 7.66-7.70 (m, 3H), 7.28-7.39 (m, 3H), 7.11 (m, 1H), 4.04 (s,3H), 2.24 (d, 3H); EI/MS 471 m/e (M+1).

[0185]3-(2-Chloro-6-fluorophenyl)-5-[2,4-dimethyl-5-(2-fluoro-4-trifluoromethyl-phenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0186] Product was obtained as a yellow semi-solid (21% yield): ¹H NMR(CDCl₃) δ 7.43-7.53 (m, 3H), 7.29-7.39 (m, 2H), 7.11 (m, 1H), 3.90 (s,3H), 2.44 (s, 3H), 2.04 (d, 3H); EI/MS 484 m/e (M⁺).

[0187]3-(2-Chloro-6-fluorophenyl)-5-[2,4-dimethyl-5-(4-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0188] Product was isolated as a white solid (5% yield): mp 146-147° C.;¹H NMR (CDCl₃) δ 7.67 (d, 2H), 7.56 (d, 2H), 7.29-7.39 (m, 2H), 7.12 (m,1H), 3.90 (s, 3H), 2.43 (s, 3H), 2.16 (d, 3H); EI/MS 466 m/e (M⁺).

[0189]3-(2-Chloro-6-fluorophenyl)-5-[2,4-dimethyl-5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0190] Product was isolated as white needles (41% yield): mp 148-149°C.; ¹H NMR (CDCl₃) δ 7.29-7.38 (m, 4H), 7.11 (m, 1H), 6.93 (d, 2H), 4.07(q, 2H), 3.88 (s, 3H), 2.39 (s, 3H), 2.11 (s, 3H), 1.44 (t, 3H); EI/MS442 m/e (M⁺); Calcd. for C₂₃H₂₁ClN₃OS: C, 62.4; H, 4.79; N, 9.51; Found:C, 62.4; H, 4.87; N, 9.42.

[0191]3-(2-Chloro-6-fluorophenyl)-5-[4-chloro-5-(2-fluoro-4-trifluoromethoxyphenyl)-thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0192] Product was obtained as a white solid (64% yield): mp 112-116°C.; ¹H NMR (CDCl₃) δ 7.72 (t, J=4.3 Hz, 3H), 7.40-7.30 (m, 4H),7.15-7.09 (m, 1H), 4.09 (s, 3H); EI/MS 487 m/e (M⁺); Calcd. forC₂₀H₁₁Cl₂F₄N₃OS: C, 49.20; H, 2.27; N, 8.61; Found: C, 48.95; H, 2.24;N, 8.48.

[0193]3-(2-Chloro-6-fluorophenyl)-5-[4-chloro-5-(4-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0194] Product was isolated as a white solid (66% yield): mp 88-92° C.;¹H NMR (CDCl₃) δ 7.82 (d, J=8.0 Hz, 2H), 7.76 (s, 1H), 7.74 (d, J=8.0Hz, 2H), 7.40-7.30 (m, 2H), 7.15-7.09 (m, 1H), 6.96-6.92 (m, 1H), 4.02(m, 3H). EI/MS 471 m/e (M⁺); Calcd. for C₂₀H₁₁Cl₂F₄N₃S: C, 50.86; H,2.35; N, 8.90; Found: C, 50.81; H, 2.39; N, 8.77.

[0195]3-(2-Chloro-6-fluorophenyl)-5-[4-chloro-5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0196] Product was isolated as a light yellow solid (77% yield): mp120-128° C.; ¹H NMR (CDCl₃) δ 7.63-7.58 (m, 3H), 7.39-7.29 (m, 2H),7.14-7.08 (m, 1H), 7.01-6.96 (m, 2H), 4.09 (q, J=6.9 Hz, 2H), 4.00 (s,3H), 1.45 (t, J=6.9 Hz, 3H); EI/MS 447 m/e (M⁺).

[0197]3-(2-Chloro-6-fluorophenyl)-5-{4-methyl-5-[4-(1,1,2,2-tetrafluoroethoxy)-phenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

[0198] Product was isolated as a yellow gum (28% yield): ¹H NMR (CDCl₃)δ 7.55 (s, 1H); 7.48 (d, 2H), 7.28-7.39 (m, 4H), 7.11 (m, 1H), 6.12,5.94, 5.77 (tt, J=53.2 Hz, 1H), 4.03 (s, 3H), 2.33 (s, 3H); EI/MS 500m/e (M⁺).

[0199]3-(2-Chloro-6-fluorophenyl)-5-[5-(4-fluorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0200] Product was isolated as a yellow solid (31% yield): mp 112-113°C.; ¹H NMR (CDCl₃) δ 7.52 (s, 1H), 7.41-7.46 (m, 2H), 7.29-7.39 (m, 2H),7.08-7.17 (m, 3H), 4.03 (s, 3H), 2.31 (s, 3H); EI/MS 401 m/e (M−1);Calcd. for C₂₀H₁₄ClF₂N₃S: C, 59.8; H, 3.51; N, 10.5; Found: C, 59.6; H,3.66; N, 10.4.

[0201]3-(2-Chloro-6-fluorophenyl)-5-[5-(2,4-difluorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0202] Product was isolated as a white solid (44% yield): mp 112-113°C.; ¹H NMR (CDCl₃) δ 7.62 (s, 1H), 7.29-7.39 (m, 3H), 7.11 (s, 1H),6.92-7.00 (m, 2H), 4.04 (s, 3H), 2.21 (d, 3H); EI/MS 420 m/e (M⁺);Calcd. for C₂₀H₁₃ClF₃N₃S: C, 57.2; H, 3.12; N, 10.0; Found: C, 57.2; H,3.21; N, 9.95.

[0203]3-(2-Chloro-6-fluorophenyl)-5-[5-(4-chloro-3-fluorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0204] Product was isolated as a yellow solid (47% yield): mp 132° C.;¹H NMR (CDCl₃) δ 7.56 (s, 1H), 7.47 (t, 1H), 7.27-7.37 (m, 2H),7.19-7.25 (m, 2H), 7.11 (t, 1H), 4.03 (s, 3H), 2.33 (s, 3H); EI/MS 436m/e (M⁺); Calcd. for C₂₀H₁₃Cl₂F₂N₃S: C, 55.1; H, 3.00; N, 9.63; Found:C, 55.3; H, 3.10; N, 9.47.

[0205]3-(2-Chloro-6-fluorophenyl)-5-[5-(4-chloro-2-fluorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0206] Product was isolated as a yellow foam (24% yield): ¹H NMR (CDCl₃)δ 7.63 (s, 1H), 7.29-7.39 (m, 3H), 7.21-7.24 (m, 2H), 7.11 (t, 1H), 4.03(s, 3H), 2.21 (d, 3H); EI/MS 436 m/e (M⁺); Calcd. for C₂₀H₁₃Cl₂F₂N₃S: C,55.1; H, 3.00; N, 9.63; Found: C, 55.0; H, 3.09; N, 9.47.

[0207]3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-3-trifluoromethyl)phenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0208] Product was isolated as a yellowish solid (54% yield): mp127-128° C.; ¹H NMR (CDCl₃) δ 7.57-7.69 (m, 3H), 7.29-7.39 (m, 3H), 7.11(t, 1H), 4.04 (s, 3H), 2.23 (d, 3H); EI/MS 470 m/e (M⁺).

[0209]3-(2-Chloro-6-fluorophenyl)-5-[5-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0210] Product was isolated as a white solid (55% yield): mp 134-135°C.; ¹H NMR (CDCl₃) δ 7.47 (s, 1H), 7.28-7.38 (m, 2H), 7.10 (t, 1H),6.99-6.96 (d, 1H), 6.94 (ds, 2H), 4.30 (s, 4H), 4.02 (s, 3H), 2.31 (s,3H); EI/MS 442 m/e (M⁺); Calcd. for C₂₂H₁₇ClFN₃O₂S: C, 59.8; H, 3.88; N,9.51; Found: C, 59.7; H, 4.06; N, 9.45.

[0211]3-(2-Chloro-6-fluorophenyl)-5-[5-(1,3-benzodioxin-5-yl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0212] Product was isolated as white crystals (61% yield): mp 122-123°C.; ¹H NMR (CDCl₃) δ 7.47 (s, 1H), 7.28-7.38 (m, 2H), 7.10 (d, 2H),6.92-6.96 (m, 2H), 6.87 (d, 2H), 6.01 (d, 2H), 4.02 (s, 3H), 2.30 (s,3H); EI/MS 428 m/e (M⁺).

[0213]3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-methoxyethoxy)phenyl]-4-methyl-thien-3-yl}-1-methyl-1H-1,2,4-triazole

[0214] Product was isolated as a pale yellow glass (32% yield): ¹H NMR(CDCl₃) δ 7.48 (s, 1H), 7.39 (d, 2H), 7.29-7.38 (m, 2H), 7.11 (t, 1H),7.00 (d, 2H), 4.17 (m, 2H), 4.02 (s, 3H), 3.79 (m, 2H), 3.47 (s, 3H),2.30 (s, 3H); EI/MS 457 m/e (M−1).

[0215]3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-methylpropenyloxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-1,2,4-triazole

[0216] Product was isolated as a pale liquid (11% yield): ¹H NMR (CDCl₃)δ 7.48 (s, 1H), 7.39 (d, 2H), 7.28-7.37 (m, 2H), 7.10 (t, 1H), 6.98 (d,2H), 6.01-6.14 (m, 1H), 5.44 (d, 1H), 5.31 (d, 1H), 4.58 (d, 2H), 4.02(s, 3H), 2.34 (s, 3H); EI/MS 439 m/e (M−CH₃).

[0217]3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(1-methylethoxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-1,2,4-triazole

[0218] Product was isolated as a hard, yellowish glass (40% yield): ¹HNMR (CDCl₃) δ 7.52 (s, 1H), 7.29-7.39 (m, 3H), 7.11 (t, 1H), 6.99-7.05(m, 2H), 6.89 (d, 1H), 4.59 (pentet, 1H), 4.03 (s, 3H), 2.35 (s, 3H),1.36 (d, 6H); EI/MS 441 m/e (M−1); Calcd. for C₂₃H₂₁ClFN₃OS: C, 62.5; H,4.79; N, 9.51; Found: C, 62.7; H, 4.79; N, 9.50.

[0219]3-(2-Chloro-6-fluorophenyl)-5-[5-(2,4-dichlorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0220] Product was isolated as white crystals (4% yield): mp 114-115°C.; ¹H NMR (CDCl₃) δ 7.62 (s, 1H), 7.53 (s, 1H), 7.29-7.39 (m, 4H), 7.11(t, 1H), 4.04 (s, 3H), 2.14 (s, 3H); EI/MS 453 m/e (M⁺); Calcd. forC₂₀H₁₃Cl₃FN₃S: C, 53.1; H, 2.89; N, 9.28; Found: C, 52.9; H, 3.30; N,8.86.

[0221]3-(2-Chloro-6-fluorophenyl)-5-[5-(3,4-dichlorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0222] Product was isolated as a white solid (48% yield): mp 138° C.; ¹HNMR (CDCl₃) δ 7.54 (d, 2H), 7.51 (s, 1H), 7.29-7.39 (m, 4H), 7.11 (t,1H), 4.03 (s, 3H), 2.33 (s, 3H); EI/MS 452 m/e (M−1); Calcd. forC₂₀H₁₃Cl₃FN₃S: C, 53.1; H, 2.89; N, 9.28; Found: C, 53.1; H, 3.05; N,9.24.

[0223]3-(2-chloro-6-fluorophenyl)-5-[3-methyl-5-(4-trifluoromethoxyphenyl)-thien-2-yl]-1-methyl-1H-1,2,4-triazole

[0224] Product was isolated as a tan solid (72% yield): mp 96-97° C.; ¹HNMR (CDCl₃) δ 2.41 (s, 3H), 4.05 (s, 3H), 7.07 (m, 1H), 7.21-7.38 (m,5H), 7.62 (d, 2H); EI/MS 467 m/e (M+).

[0225]3-(2-Chloro-6-fluorophenyl)-5-{3-methyl-5-[4-(trifluoromethyl)phenyl]-thien-2-yl}-1-methyl-1H-1,2,4-triazole

[0226] Product was isolated as an off-white solid (70% yield): mp 85-86°C.; ¹H NMR (CDCl₃) δ 2.43 (s, 3H), 4.12 (s, 3H), 7.10 (m, 1H), 7.25-7.41(m, 3H), 7.72 (q, 4H, J=8.3 Hz); EI/MS 451 m/e (M+).

[0227]3-(2-Chloro-6-fluorophenyl)yl-5-[3-methyl-5-(3-chloro-4-fluorophenyl)-thien-2-yl]-1-methyl-1H-1,2,4-triazole

[0228] Product was isolated as a tan solid (58% yield): mp 121-122° C.;¹H NMR (CDCl₃) δ 2.25 (s, 3H), 3.95 (s, 3H), 6.95-7.22 (m, 5H), 7.31 (m,1H), 7.55 (d, 2H); EI/MS 436 m/e (M+).

[0229]3-(2,6-difluorophenyl)-5-{3-chloro-5-[4-(trifluoromethoxy)phenyl]thien-2-yl}-1-methyl-1H-1,2,4-triazole

[0230] Product was isolated as a yellow solid (65% yield): mp 105-107°C.; ¹H NMR (CDCl₃) δ 7.63-7.59 (m, 2H), 7.41-7.36 (m, 1H), 7.30-7.25 (m,3H), 7.06-7.00 (m, 2H), 4.07 (s, 3H); EI/MS 471 m/e (M+); Calcd forC₂₀H₁₁ClF₅N₃OS: C, 50.91; H, 2.35; N, 8.91; S, 6.80; Found: C, 50.90; H,2.44; N, 8.64; S, 6.93.

[0231]3-(2,6-Difluorophenyl)-5-[3-chloro-5-(4-methylphenyl)thien-2-yl]-1-methyl-1H-1,2,4-triazole

[0232] Product was isolated as an off-white foamy solid (69% yield): mp139-141° C.; ¹H NMR (CDCl₃) δ 7.47 (m, 2H), 7.41-7.35 (m, 1H), 7.26-7.22(m, 3H), 7.05-7.02 (m, 2H), 4.07 (s, 3H), 2.39 (s, 3H); EI/MS 401 m/e(M+); Calcd for C₂₀H₁₄ClF₂N₃S: C, 59.78; H, 3.51; N, 10.46; S, 7.98;Found: C, 59.83; H, 3.61; N, 10.22; S, 8.16.

[0233]3-(2,6-Difluorophenyl)-5-[3-chloro-5-(4-ethoxyphenyl)thien-2-yl]-1-methyl-1H-1,2,4-triazole

[0234] Product was isolated as a light yellow solid (64% yield): mp120-123° C.; ¹H NMR (CDCl₃) δ 7.50 (d, 2H, J=8.7 Hz), 7.38 (m, 1H), 7.15(s, 1H), 7.05-6.99 (m, 2H), 6.94 (d, 2H, J=8.7 Hz), 4.06 (m, 5H), 1.44(t, 3H, J=6.9 Hz); EI/MS 432 m/e (M+H); Calcd for C₂₁H₁₆ClF₂N₃OS: C,58.40; H, 3.73; N, 9.73; S, 7.42; Found: C, 58.44; H, 3.88; N, 9.48; S,7.23.

[0235]3-(2,6-Difluorophenyl)-5-{3-chloro-5-[4-trifluoromethyl)phenyl]thien-2-yl}-1-methyl-1H-1,2,4-triazole

[0236] Product was isolated as a white solid (63% yield): mp 156-162°C.; ¹H NMR (CDCl₃) δ 7.70 (s, 4H), 7.42-7.35 (m, 2H), 7.03 (t, 2H,J=8.05 Hz), 4.08 (s, 3H); EI/MS 455 m/e (M+); Calcd for C₂₀H₁₁ClF₅N₃S:C, 52.70; H, 2.43; N, 9.22; S, 7.03; Found: C, 52.81; H, 2.50; N, 9.13;S, 7.11.

[0237]3-(2-Chloro-6-fluorophenyl)-5-{3-chloro-5-[4-trifluoromethoxy)phenyl]thien-2-yl}-1-methyl-1H-1,2,4-triazole

[0238] Product was isolated as an off-white solid (62% yield): mp120-123° C.; ¹H NMR (CDCl₃) δ 7.62 (ddd, 2H, J=2.1, 2.9, 8.7 Hz),7.40-7.26 (m, 5H), 7.15-7.08 (m, 1H), 4.08 (s, 3H); EI/MS 487 m/e (M+);Calcd for C₂₀H₁₁Cl₂F₄N₃OS: C, 49.20; H, 2.27; N, 8.61; S, 6.57; Found:C, 49.42; H, 2.38; N, 8.37; S, 6.61.

[0239]3-(2-Chloro-6-fluorophenyl)-5-{3-chloro-5-[4-(trifluoromethyl)phenyl]thien-2-yl}-1-methyl-1H-1,2,4-triazole

[0240] Product was isolated as an off-white solid (60% yield): mp133-136° C.; ¹H NMR (CDCl₃) δ 7.70 (s, 4H), 7.38-7.30 (m, 3H), 7.15-7.09(m, 1H), 4.09 (s, 3H); EI/MS 471 m/e (M+); Calcd for C₂₀H₁₁Cl₂F₄N₃S: C,50.86; H, 2.35; N, 8.90; S, 6.79; Found: C, 51.01; H, 2.36; N, 8.67; S,6.48.

[0241]3-(2-Chloro-6-fluorophenyl)-5-[3-chloro-5-(4-methylphenyl)thien-2-yl]-1-methyl-1H-1,2,4-triazole

[0242] Product was isolated as a light yellow solid (69% yield): mp111-115° C.; ¹H NMR (MHz, CDCl₃) δ 7.49 (d, 2H, J=8.0 Hz), 7.46-7.23 (m,5H), 7.14-7.08 (m, 1H), 4.09 (s, 3H); EI/MS 417 m/e (M+); Calcd forC₂₀H₁₄Cl₂FN₃S: C, 57.43; H, 3.37; N, 10.04; S, 7.66; Found: C, 57.19; H,3.46; N, 9.64; S, 7.16.

[0243]3-(2-Chloro-6-fluorophenyl)-5-[3-chloro-5-(4-ethoxyphenyl)thien-2-yl]-1-methyl-1H-1,2,4-triazole

[0244] Product was isolated as an off-white solid (66% yield): mp126-128° C.; ¹H NMR (CDCl₃) δ 7.50 (dd, 2H, J=8.7, 2.0 Hz), 7.39-7.29(m, 2H), 7.15 (s, 1H), 7.14-7.08 (m, 1H), 6.96-6.92 (m, 1H), 4.11 (m,5H), 1.44 (t, 3H, J=7.1 Hz); EI/MS 419 m/e (M-Et); Calcd forC₂₁H₁₆Cl₂FN₃OS: C, 56.26; H, 3.60; N, 9.37; S, 7.15; Found: C, 56.33; H,3.62; N, 9.31; S, 7.13.

[0245]3-(2-Chloro-6-fluorophenyl)-5-[5-(4-bromophenyl)-3-chlorothien-2-yl]-1-methyl-1H-1,2,4-triazole

[0246] Product was isolated as an off-white solid (44% yield): mp126-128° C.; ¹H NMR (CDCl₃) δ 7.57 (d, 2H, J=8.4 Hz), 7.46 (d, 2H, J=8.4Hz), 7.37-7.29 (m, 2H), 7.26 (s, 1H and CDCl₃), 7.14-7.08 (m, 1H), 4.08(s, 3H); EI/MS 483 m/e (M+); Calcd for C₁₉H₁₁BrCl₂FN₃S: C, 47.23; H,2.29; N, 8.70; S, 6.64; Found: C, 47.32; H, 2.34; N, 8.46; S, 6.68.

[0247]3-(2-Chloro-6-fluorophenyl)-5-{3-chloro-5-[4-(methylthio)phenyl]thien-2-yl}-1-methyl-1H-1,2,4-triazole

[0248] Product was isolated as a light yellow solid (66% yield): mp125-126° C.; ¹H NMR (CDCl₃) δ 7.50 (d, 2H, J=8.7 Hz), 7.40-7.23 (m, 5H),7.14-7.08 (m, 1H), 4.08 (s, 3H), 2.52 (s, 3H); EI/MS 449 m/e (M+); Calcdfor C₂₀H₁₄Cl₂FN₃S₂: C, 53.34; H, 3.13; N, 9.33; S, 14.24; Found: C,53.17; H, 3.19; N, 9.19; S, 14.28.

[0249]3-(2-Chloro-6-fluorophenyl)-5-{4-bromo-3-chloro-5-[4-(trifluoromethoxy)-phenyl]thien-2-yl}-1-methyl-1H-1,2,4-triazole

[0250] Product was isolated as a white solid (18%): mp 170-172° C.; ¹HNMR (CDCl₃) δ 7.69 (d, 2H, J=8.7 Hz), 7.38-7.29 (m, 4H), 7.23-7.09 (m,1H), 4.09 (s, 3H); EI/MS 567 m/e (M+).

[0251]3-(2-Chloro-6-fluorophenyl)-5-{4-bromo-3-chloro-5-[4-(trifluoromethyl)phenyl]-thien-2-yl}-1-methyl-1H-1,2,4-triazole

[0252] Product was isolated as a white solid (28% yield): mp 167-170°C.; ¹H NMR (CDCl₃) δ 7.50 (dd, 2H, J=8.7, 2.0 Hz), 7.39-7.29 (m, 2H),7.15 (s, 1H), 7.14-7.08 (m, 1H), 6.96-6.92 (m, 1H), 4.11 (m, 5H), 1.44(t, 3H, J=7.1 Hz); EI/MS 551 m/e (M+).

[0253]3-(2-Chloro-6-fluorophenyl)-5-[4-bromo-3-chloro-5-(4-ethoxyphenyl)thien-2-yl]-1-methyl-1H-1,2,4-triazole

[0254] Product was isolated as a white solid (41% yield): mp 145-150°C.; ¹H NMR (CDCl₃) δ 7.58 (d, 2H, J=8.7 Hz), 7.40-7.30 (m, 2H),7.14-7.08 (m, 1H), 6.99 (d, 2H, J=8.7 Hz), 4.13-4.03 (m, 5H), 1.45 (t,3H, J=6.9 Hz); EI/MS m/e 527 (M+).

[0255]3-(2-Chloro-6-fluorophenyl)-5-[4-(4-trifluoromethoxyphenyl)-3-methylthien-2-yl]-1-methyl-1H-1,2,4-triazole

[0256] Product was isolated as an off-white solid (69% yield): mp108-109° C.; ¹H NMR (CDCl₃) δ 2.16 (s, 3H), 3.92 (s, 3H), 6.96 (m, 1H),7.11-7.29 (m, 7H); EI/MS 467 m/e (M⁺)

[0257]3-(2-Chloro-6-fluorophenyl)-5-[4-(4-ethoxyphenyl)-3-methylthien-2-yl]-1-methyl-1H-1,2,4-triazole

[0258] Product was isolated as an off-white solid (80% yield): mp124-127° C.; ¹H NMR (CDCl₃) δ 1.45 (t, 3H, J=7.0 Hz), 2.31 (s, 3H), 4.06(s, 3H), 6.96 (d, 2H, J=8.4 Hz), 6.98-7.13 (m, 1H), 7.30-7.39 (m, 5H);EI/MS 427 m/e (M+H); Calcd. for C₂₂H₁₉ClFN₃OS: C, 61.75; H, 4.48; N,9.82; Found: C, 61.74; H, 4.53; N, 9.63.

[0259]3-(2-Chloro-6-fluorophenyl)-5-[4-(4-trifluoromethylphenyl)-3-methylthien-2-yl]-1-methyl-1H-1,2,4-triazole

[0260] Product was isolated as a white solid (66% yield): mp 102-103°C.; ¹H NMR (CDCl₃) δ 2.34 (s, 3H), 4.08 (s, 3H), 7.10 (dd, 1H, J=7.3Hz), 7.31-7.38 (m, 2H), 7.49 (s, 1H), 7.53 (d, 2H, J=8.0 Hz), 7.71 (d,2H, J=8.0 Hz); EI/MS 467 m/e (M⁺).

[0261]3-(2-Chloro-6-fluorophenyl)-5-[4-(4-isopropylphenyl)-3-methylthien-2-yl]-1-methyl-1H-1,2,4-triazole

[0262] Product was isolated as a white solid (53% yield): mp 109-111°C.; ¹H NMR (CDCl₃) δ 1.30 (d, 6H, J=6.6 Hz), 2.33 (s, 3H), 2.96 (m, 1H),4.06 (s, 3H), 7.08-7.14 (m, 1H), 7.28-7.38 (m, 7H); EI/MS 425 m/e (M+H);Calcd. for C₂₃H₂₃ClFN₃S: C, 64.86; H, 4.97; N, 9.86; Found: C, 64.51; H,5.02; N, 9.78.

[0263]3-(2-Methylphenyl)-5-{4-methyl-5-[4-trifluoromethoxyphenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

[0264] Product was obtained as a yellowish solid (83% yield): mp122-123° C.; ¹H NMR (CDCl₃) δ 7.98-8.01 (m, 1H), 7.48-7.52 (m, 3H),7.27-7.32 (m, 5H), 3.98 (s, 3H), 2.69 (s, 3H), 2.33 (s, 3H); EI/MS 430m/e (M+1).

[0265]3-(2-Methylphenyl)-5-{4-methyl-5-[4-trifluoromethylphenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

[0266] Product was obtained as a yellow solid (68% yield): mp 149-150°C.; ¹H NMR (CDCl₃) δ 7.98-8.00 (m, 1H), 7.71 (d, J=8.1 Hz, 2H), 7.61 (d,J=8.4 Hz, 2H), 7.56 (s, 1H), 7.27-7.30 (m, 3H), 3.99 (s, 3H), 2.69 (s,3H), 2.36 (s, 3H); EI/MS 414 m/e (M+1).

[0267]3-(2-Methylphenyl)-5-[5-(4-ethoxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0268] Product was obtained as white needles (11% yield): mp 160-161°C.; ¹H NMR (CDCl₃) δ 7.98-8.01 (m, 1H), 7.44 (s, 1H), 7.29-7.43 (m, 2H),7.26-7.29 (m, 3H), 6.94-6.99 (m, 2H), 4.08 (q, J=6.9 Hz, 2H), 3.98 (s,3H), 2.69 (s, 3H), 2.31 (s, 3H), 1.45 (t, J=7.2 Hz, 3H); EI/MS 390 m/e(M+1).

Example 2

[0269]3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(3-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0270] A solution of3-(2-chloro-6-fluorophenyl)-1-methyl-5-[5-(3-trifluoromethyl-phenyl)thien-3-yl]-1H-1,2,4-triazole(0.45 g, 1 mmol) and N-chlorosuccinimide (0.15 g, 1.1 mmol) in methylenechloride/glacial acetic acid (1:1, 2 mL) was refluxed under nitrogen for2 days, cooled to room temperature, poured into water (10 mL) andextracted with ether (3×20 mL). The combined ethereal extracts werewashed with water (3×30 mL), saturated aqueous sodium bicarbonate (50mL) and brine (30 mL), dried over magnesium sulphate and chromatographedon silica to afford the product as a white solid (0.37 g, 76%): mp53-54° C.; ¹H NMR (CDCl₃) δ 7.79 (s, 1H), 7.71 (d, 2H), 7.60 (d, 1H),7.54 (t, 1H), 7.44 (s, 1H), 7.30-7.40 (m, 2H), 7.11 (t, 1H), 4.05 (s,3H); EI/MS 472 m/e (M⁺); Calcd. for C₂₀H₁₁Cl₂F₄N₃S: C, 50.9; H, 2.35; N,8.90; Found: C, 50.9; H, 2.49; N, 8.82.

[0271] The following compounds were prepared according to the generalprocedure of Example 2.

[0272]3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(3-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0273] Product was isolated as a white solid (96% yield): mp 98-99° C.;¹H NMR (CDCl₃) δ 7.29-7.46 (m, 6H), 7.21 (br, 1H), 7.11 (t, 1H), 4.04(s, 3H); EI/MS 488 m/e (M⁺); Calcd. for C₂₀H₁₁Cl₂F₄N₃OS: C, 49.2; H,2.27; N, 8.61; Found: C, 49.4; H, 2.40; N, 8.49.

[0274]3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(2-fluoro-4-trifluoromethylphenyl)-thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0275] Product was isolated as a white solid (66% yield): mp 157-158°C.; ¹H NMR (CDCl₃) δ 7.72 (t, 1H), 7.62 (s, 1H), 7.44-7.49 (m, 2H),7.33-7.38 (m, 2H), 7.12 (t, 1H), 4.04 (s, 3H); EI/MS 490 m/e (M⁺);Calcd. for C₂₀H₁₀Cl₂F₅N₃S: C, 49.0; H, 2.06; N, 8.57; Found: C, 48.5; H,2.29; N, 8.34.

[0276]3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(4-chloro-2-fluorophenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0277] Product was isolated as white, iridescent flakes (57% yield): mp197-198° C.; ¹H NMR (CDCl₃) δ 7.49-7.54 (m, 2H), 7.29-7.38 (m, 2H),7.18-7.24 (m, 2H), 7.11 (t, 1H), 4.04 (s, 3H); EI/MS 458 m/e (M+1);Calcd. for C₁₉H₁₀Cl₃F₂N₃S; C, 50.0; H, 2.21; N, 9.20; Found: C, 49.6; H,2.31; N, 8.94.

[0278]3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(4-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0279] Product was isolated as an amorphous white solid (64% yield): mp145-146° C.;

[0280]¹H NMR (CDCl₃) δ 7.66 (dd, 4H), 7.46 (s, 1H), 7.30-7.40 (m, 2H),7.12 (m, 1H), 4.05 (s, 3H); EI/MS 472 m/e (M⁺).

[0281]3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0282] Product was isolated as needles (12% yield): mp 154-155° C.; ¹HNMR (CDCl₃) δ 7.56 (d, 2H), 7.30-7.40 (m, 2H), 7.25-7.28 (m, 3H), 7.11(m, 1H), 4.04 (s, 3H); EI/MS 488 m/e (M⁺).

Example 3

[0283]3-(2-Chloro-6-fluorophenyl)-5-[2-bromo-5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0284] A solution of3-(2-chloro-6-fluorophenyl)-1-methyl-5-[5-(4-trifluoromethoxy-phenyl)thien-3-yl]-1H-1,2,4-triazole(0.26 g, 0.6 mmol) in glacial acetic acid (7 mL) was cooled to 6° C.Bromine (0.1 g, 32 μL, 0.6 mmol) was added to the reaction and allowedto warm to room temperature and stirred for 16 hours. The reactionmixture was poured into water (50 mL) and extracted with ether (3×30mL). The combined ethereal extracts were washed with water (100 mL),saturated aqueous sodium bicarbonate (100 mL), aqueous sodium bisulphite(10% solution, 50 mL) and brine (70 mL), dried over magnesium sulphateand concentrated. Column chromatography gave the product (297 mg, 97%)as a yellowish solid: mp 135-136° C.; ¹H NMR (CDCl₃) δ 7.57 (d, 1H),7.25-7.40 (m, 5H), 7.12 (t, 1H), 4.04 (s, 3H); EI/MS 533 m/e (M⁺).

[0285] The following compounds were prepared according to the generalprocedure of Example 3.

[0286]3-(2-Chloro-6-fluorophenyl)-5-[2-bromo-4-methyl-5-(4-trifluoromethoxyphenyl)-thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0287] Product was isolated as a clear, thick gum (99% yield): ¹H NMR(CDCl₃) δ 7.42 (d, 2H), 7.27-7.31 (m, 4H), 7.10 (t, 1H), 3.97 (s, 3H),2.18 (s, 3H); EI/MS 547 m/e (M⁺).

Example 4

[0288]3-(2-Chloro-6-fluorophenyl)-5-[2-methyl-5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0289] n-Butyllithium (2.5 N in hexanes, 0.25 mL, 0.4 mmol) was added toa solution of3-(2-chloro-6-fluorophenyl)-5-[2-bromo-5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole(190 mg, 0.3 mmol) in dry THF (2 mL) at −75° C. and stirred for 1 hour.Iodomethane (66 mg, 29 μL, 0.5 mmol) was added to this reaction mixtureand stirred at −75° C. for 30 minutes. After warming to 0° C., saturatedaqueous ammonium chloride (2 mL) was added, followed by water (30 mL)and the mixture was extracted with ether (3×10 mL). The combinedethereal extracts were washed with water (30 mL) and brine (10 mL),dried over magnesium sulphate and chromatographed on silica to give theproduct (49 mg, 29%) as a yellow solid: mp 153-155° C.; ¹H NMR (CDCl₃) δ7.59 (d, 2H), 7.29-7.39 (m, 3H), 7.25 (d, 2H), 7.12 (t, 1H), 4.01 (s,3H), 2.62 (s, 3H); EI/MS 467 m/e (M−1).

[0290] The following compounds were prepared according to the generalprocedure of Example 4.

[0291]3-(2-Chloro-6-fluorophenyl)-5-[2,4-dimethyl-5-(4-trifluoromethoxyphenol)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0292] Product was isolated as a hard, colourless glass (59% yield): ¹HNMR (CDCl₃) δ 7.45-7.47 (d, 2H), 7.28-7.40 (m, 4H), 7.12 (t, 1H), 3.98(s, 3H), 2.41 (s, 3H), 2.13 (s, 3H); EI/MS 481 m/e (M−1).

[0293]3-(2-Chloro-6-fluorolphenyl)-5-[2-chloro-4-methyl-5-(4-trifluoromethoxyphenyl)-thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0294] Product was isolated as a colourless gum (65% yield): ¹H NMR(CDCl₃) δ 7.45 (d, 2H), 7.28-7.38 (m, 4H), 7.12 (t, 1H), 3.98 (s, 3H),2.18 (s, 3H); EI/MS 501 m/e (M−1).

Example 5

[0295]3-(2-Chloro-6-fluorophenyl)-5-[(5-(4-fluoromethylthio)phenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0296] A solution of3-(2-chloro-6-fluorophenyl)-5-[4-methyl-5-(4-methylsulfinylphenyl)-thien-3-yl]-1-methyl-1H-1,2,4-triazole (160 mg, 0.36 mmol) inchloroform (4 mL) was treated with (diethylamino)sulphur trifluoride (77mg, 0.5 mmol) and antimony trifluoride (1.1 mg, 4.8 mol). Suspendedsolids gradually dissolved upon stirring at room temperature. Saturatedaqueous sodium bicarbonate (3 mL) and 50% aqueous sodium hydroxide (1drop via Pasteur pipette) were added after 5 hours stirring at roomtemperature. The organic phase was collected and the aqueous phase wasextracted with chloroform (2×10 mL). The combined organic extracts werewashed with water (10 mL), saturated sodium bicarbonate (10 mL) andbrine (10 mL), dried over magnesium sulphate and chromatographed onsilica gel to furnish the target compound (22 mg, 37%): ¹H NMR (CDCl₃) δ7.55-7.58 (m, 3H), 7.46 (d, 2H), 7.29-7.39 (m, 2H), 7.11 (t, 1H), 5.86(s, 1H), 5.69 (s, 1H), 4.03 (s, 3H), 2.34 (s, 3H); EI/MS 447 m/e (M+1).

Example K

[0297]4-{4-Chloro-5-[3-(2-chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazol-5-yl]thien-2-yl}phenol

[0298]5-[3-Chloro-5-(4-ethoxyphenyl)thien-2-yl]-3-(2-chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazole(542 mg, 1.20 mmol) was dissolved in CH₂Cl₂ (12 mL) under N₂ and wascooled to 0° C. To this was added BBr₃ (1.0 M solution in CH₂Cl₂; 2.0mL, 2.0 mmol) dropwise via syringe. The cooling bath was removedimmediately and the reaction mixture was allowed to warm to 25° C. andstirred for 20 hours. The mixture was poured onto H₂O (100 mL) andstirred at 25° C. for 30 min. The layers were partitioned, and theaqueous layer was extracted with CH₂Cl₂ (2×50 mL). The combined organicextracts were washed with H₂O (50 mL) and satd aq NaCl (50 mL), dried(Na₂SO₄), filtered and concentrated. Column chromatography (10-80%Et₂O-hexanes) gave the product (414 mg, 81%) as a light yellow solid: mp205-209° C.; ¹H NMR (CDCl₃) δ 7.38 (m, 2H), 7.34-7.25 (m, 2H), 7.09-7.03(m, 2H), 6.80 (m, 2H), 4.00 (s, 3H); EI/MS 420 m/e (M+).

[0299] The following compounds were prepared according to the generalprocedure of Example K.

[0300]3-(2-Chloro-6-fluorophenyl)-5-[5-(4-hydroxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0301] Product was isolated as white plates (42% yield): mp 221-222° C.;¹H NMR (CDCl₃) δ 7.47 (s, 1H), 7.26-7.37 (m, 4H), 7.11 (t, 1H), 6.84 (d,2H), 5.77 (br, 1H), 4.02 (s, 3H), 2.25 (s, 3H); EI/MS 399 m/e (M−1).

[0302]4-{3-Chloro-4-[3-(2-chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazol-5-yl]thien-2-yl}phenol

[0303] Product was isolated as a salmon-colored solid (27% yield): mp239-242° C.; ¹H NMR (CDCl₃) δ 7.59 (s, 1H), 7.49 (d, 2H, J=8.05 Hz),7.35-7.28 (m, 2H), 7.15-7.10 (m, 1H), 6.85 (d, 2H, J=8.42), 6.31 (bs,1H), 4.00 (s, 3H); EI/MS 420 m/e (M+H), 418 m/e (M−H).

[0304]4-{5-[3-(2-Chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazol-5-yl]-4-methylthien-3-yl}phenol

[0305] Product was isolated as an off-white solid (50% yield): mp233-235° C.; ¹H NMR (CDCl₃) δ 2.29 (s, 3H), 4.06 (s, 3H), 5.03 (s, 1H),6.88 (d, 2H, J=8.4 Hz), 7.08-7.13 (m, 1H), 7.24-7.27 (m, 3H), 7.30-7.36(m, 2H); EI/MS 399 m/e (M−H); Calcd. for C₂₀H₁₅ClFN₃OS: C, 60.07; H,3.78; N, 10.51; Found: C, 60.06; H, 3.88; N, 10.28.

Example L

[0306]3-(2-Chloro-6-fluorophenyl)-5-[5-(4-hydroxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0307] Dilute hydrochloric acid (4 N, 2.5 mL) was added to a suspensionof3-(2-chloro-6-fluorophenyl)-5-{4-methyl-5-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole(0.62 g, 1.3 mmol) in tetrahydrofuran (2.5 mL), stirred at roomtemperature for 30 minutes, poured into water (20 mL) and extracted withether (3×20 mL). The combined ethereal extracts were washed with water(100 mL) and brine (50 mL), dried over magnesium sulphate andconcentrated under reduced pressure to leave the desired product (0.49g, 96%) as a white solid. ¹H NMR (CDCl₃) and mass spectrometry dataindicated this material to be free of impurities and to be comparable toauthentic material prepared according to that in Example K.

Example 6

[0308]3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(4-n-propoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

[0309] A solution of3-(2-chloro-6-fluorophenyl)-5-[5-(4-hydroxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole(97 mg, 0.2 mmol) in dry THF (2 mL) was cooled to −3° C. and treatedwith sodium hydride (95% suspension in mineral oil, 9 mg, 0.4 mmol).After stirring for 5 minutes, iodopropane (62 mg, 0.4 mmol) was addedand the reaction was allowed to stir at room temperature for 16 hours.An additional batch of sodium hydride (9 mg, 0.4 mmol) and iodopropane(62 mg, 0.4 mmol) was added and the reaction heated to 45° C. Afterdilution with water (5 mL), the product was extracted with ether (3×5mL). The combined ethereal extracts were washed with water (2×5 mL) andbrine (10 mL), dried over magnesium sulphate and concentrated. Columnchromatography gave the product (101 mg, 93%) as a colorless glass: ¹HNMR (CDCl₃) δ 7.49 (s, 1H), 7.27-7.41 (m, 4H), 7.12 (t, 1H), 6.98 (d,2H), 4.04 (s, 3H), 3.99 (t, 2H), 2.32 (s, 3H), 1.85 (m, 2H), 1.08 (t,3H); EI/MS 441 m/e (M+1).

[0310] The following compounds were prepared according to the generalprocedure of Example 6.

[0311]3-(2-Chloro-6-fluorophenyl)-5-{4-methyl-5-[4-(2,2,2-trifluoroethoxy)phenyl]-thien-3-yl}-1-methyl-1H-1,2,4-triazole

[0312] Product was isolated as white plates (15% yield): mp 161-162° C.;¹H NMR (CDCl₃) δ 7.62 (s, 1H), 7.57 (d, 2H), 7.32-7.39 (m, 2H), 7.11 (t,1H), 7.03 (d, 2H), 4.42 (q, 2H), 4.03 (s, 3H), 2.31 (s, 3H); EI/MS 481m/e (M+1).

[0313]3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-fluoroethoxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-1,2,4-triazole

[0314] Product was isolated as colourless cubes (43% yield): mp 121-122°C.; ¹H NMR (CDCl₃) δ 7.49 (s, 1H), 7.41 (d, 2H), 7.29-7.39 (m, 2H), 7.11(t, 1H), 7.00 (d, 2H), 4.87 (t, 1H), 4.71 (t, 1H), 4.31 (t, 1H), 4.22(s, 3H), 4.03 (s, 3H), 2.31 (s,3H); EI/MS 445 m/e (M+1).

Example 7

[0315]3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-1,2,4-triazole

[0316] A solution of3-(2-chloro-6-fluorophenyl)-5-[5-(4-hydroxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole(300 mg, 0.7 mmol) in dry DMF (3 mL) was treated with aqueous sodiumhydroxide (25% solution, 120 μL, 3.5 mmol) at a dropwise rate. Afterstirring at room temperature for 30 minutes, hexafluoropropene wasbubbled in for 35 minutes and then stirred at room temperature for 40minutes. The reactants were poured into water (50 mL) and extracted withether (3×40 mL). The combined ethereal extracts were washed with water(4×150 mL) until the aqueous washings were neutral and then with brine(100 mL), dried over magnesium sulphate, and concentrated. Columnchromatography afforded a colourless gum (0.24 g, 58%): ¹H NMR (CDCl₃) δ7.55 (s, 1H), 7.49 (d, 2H), 7.26-7.39 (m, 4H), 7.11 (t, 1H), 5.10 & 4.95(d sextets, 1H), 4.03 (s, 3H), 2.33 (s,3H); EI/MS 549 (M+1).

[0317] The following compounds were prepared according to the generalprocedure of Example 7.

[0318]3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2,2-dichloro-1,1-difluoroethoxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-1,2,4-triazole

[0319] The product was isolated as a pale, yellow foam (58% yield): ¹HNMR (CDCl₃) δ 7.54 (s, 1H), 7.48 (d, 2H), 7.29-7.39 (m, 4H), 7.11 (t,1H), 5.95 (t, 1H), 4.03 (s, 3H), 2.33 (s,3H); EI/MS 533 m/e (M⁺).

[0320]3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-chloro-1,1,2-trifluoroethoxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-1,2,4-triazole

[0321] The product was isolated as a colourless glass (78% yield): ¹HNMR (CDCl₃) δ 7.55 (s, 1H), 7.49 (d, 2H), 7.29-7.39 (m, 4H), 7.11 (t,1H), 6.38 & 6.22 (t, 1H), 4.03 (s, 3H), 2.33 (s, 3H); EI/MS 515 m/e(M−1); Calcd. for C₂₂H₁₅Cl₂F₄N₃O₂S: C, 51.3; H, 2.94; N, 8.16; S, 6.21;Found: C, 51.2; H, 3.01; N, 8.07; S, 6.21.

[0322]3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-bromo-1,1,2-trifluoroethoxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-1,2,4-triazole

[0323] The product was isolated as a white solid (76% yield): mp 80-82°C.; ¹H NMR (CDCl₃) δ 7.55 (s, 1H), 7.49 (d, 2H), 7.29-7.39 (m, 4H), 7.11(t, 1H), 6.64 & 6.48 (t, 1H), 4.03 (s, 3H), 2.33 (s, 3H); EI/MS 562 m/e(M+1).3-(2-Chloro-6-fluorophenyl)-5-[5-(4-difluoromethoxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

[0324] The product was isolated as an amorphous white solid (52% yield):mp 115-116° C.; ¹H NMR (CDCl₃) δ 7.53 (s, 1H), 7.47 (d, 2H), 7.29-7.45(m, 2H), 7.20 (d, 2H), 7.11 (t, 1H), 6.57 (t, J=73.8 Hz, 1H), 4.03 (s,3H), 2.32 (s, 3H); EI/MS 450 (M⁺).

[0325]3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-chloro-1,1,2-trifluoroethoxy)phenyl]-3-methylthien-2-yl}-1-methyl-1H-1,2,4-triazole

[0326] The product was isolated as a white solid (65% yield): mp115-116° C.; ¹H NMR (CDCl₃) δ 7.55 (d, 2H), 7.11-7.31 (m, 5H), 7.02 (t,1H), 6.13 & 6.30 (t, 1H), 3.99 (s, 3H), 2.34 (s, 3H); EI/MS 515 m/e(M−1).

[0327]3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2,2-dichloro-1,1-difluoroethoxy)phenyl]-3-methylthien-2-yl}-1-methyl-1H-1,2,4-triazole

[0328] Product was isolated as a white solid (72% yield): mp 119-120°C.; ¹H NMR (CDCl₃) δ 7.55 (d, 2H), 7.21-7.31 (m, 3H), 7.15 (s, 1H), 7.02(t, 1H), 5.85 (t, 1H), 3.99 (s, 3H), 2.34 (s, 3H); EI/MS 534 m/e (M+1).

[0329]3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-3-methylthien-2-yl}-1-methyl-1H-1,2,4-triazole

[0330] Product was isolated as a clear thick oil (58% yield): ¹H NMR(CDCl₃) δ 7.48 (d, 2H), 7.15-7.22 (m, 3H), 7.11 (s, 1H), 6.99 (t, 1H),4.79-4.95 (m, 1H), 3.93 (s, 3H), 2.27 (s, 3H); EI/MS 550 m/e (M+1).

[0331]3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-bromo-1,1,2-trifluoroethoxy)phenyl]-3-chlorothien-2-yl}-1-methyl-1H-1,2,4-triazole

[0332] Product was isolated as a white crystalline solid (68% yield): mp137-140° C.; ¹H NMR (CDCl₃) δ 7.60 (m, 2H), 7.40-7.25 (m, 5H), 7.14-7.08(m, 1H), 6.56 (dt, 1H, J_(H,F(gem))=47.6 Hz, J_(H,F(vic))=4.67 Hz,),4.08 (s, 3H); EI/MS 581 m/e (M+); Calcd for C₂₁H₁₂BrCl₂F₄N₃OS: C, 43.40;H, 2.08; N, 7.23; Found: C, 43.51; H, 2.10; N, 7.11.

[0333]3-(2-Chloro-6-fluorophenyl)-5-{4-chloro-5-[4-(2-chloro-1,1,2-trifluoroethoxy)-phenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

[0334] Product was isolated as a tan solid (71% yield): mp 82-87° C.; ¹HNMR (CDCl₃) δ 7.71 (m, 3H), 7.40-7.30 (m, 4H), 7.15-7.09 (m, 1H), 6.30(dt, 1H, J_(H,F(gem))=47.9 Hz, J_(H,F(vic)) 4.02 Hz), 4.01 (s, 3H);EI/MS 536 m/e (M+H); Calcd for C₂₁H₁₂Cl₃F₄N₃OS: C, 46.99; H, 2.25; N,7.83; Found: C, 47.06; H, 2.45; N, 7.70.

[0335]3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-chloro-1,1,2-trifluoroethoxy)phenyl]-3-chlorothien-2-yl}-1-methyl-1H-1,2,4-triazole

[0336] Product was isolated as a white solid (72% yield): mp 135-138°C.; ¹H NMR (CDCl₃) δ 7.60 (m, 2H), 7.40-7.28 (m, 5H), 7.14-7.08 (m, 1H),6.29 (dt, 1H, J_(H,F (gem))=47.9 Hz, J_(H,F(vic)) 3.93 Hz), 4.08 (s,3H); EI/MS 535 m/e (M+); Calcd for C₂₁H₁₂Cl₃F₄N₃OS: C, 46.99; H, 2.25;N, 7.83; Found: C, 46.99; H, 2.31; N, 7.69.

[0337]3-(2-Chloro-6-fluorophenyl)-5-{4-[4-(2-bromo-1,1,2-trifluoroethoxy)phenyl]-3-methylthien-2-yl}-1-methyl-1H-1,2,4-triazole

[0338] Product was isolated as a clear foam (70% yield): ¹H NMR (CDCl₃)δ 2.32 (s, 3H), 4.07 (s, 3H), 6.57 (dt, 1H, J=47.9, 4.9, 4.4 Hz),7.08-7.14 (m, 1H), 7.28-7.37 (m, 4H), 7.41 (d, 3H, J=7.3 Hz); EI/MS 560m/e (M+H); Calcd. for C₂₂H₁₅ClBrF₄N₃OS: C, 47.12; H, 2.70; N, 7.49;Found: C, 47.35; H, 2.78; N, 7.36.

[0339]3-(2-Chloro-6-fluorophenyl)-5-{4-[4-(2-chloro-1,1,2-trifluoroethoxy)phenyl]-3-methylthien-2-yl}-1-methyl-1H-1,2,4-triazole

[0340] Product was isolated as a clear oil (71% yield): ¹H NMR (CDCl₃) δ2.32 (s, 3H), 4.07 (s, 3H), 6.30 (dt, 1H, J=48.1, 4.1 Hz), 7.08-7.14 (m,1H), 7.27-7.43 (m, 7H); EI/MS 516 m/e (M+H).

[0341]3-(2-Chloro-6-fluorophenyl)-5-{4-[4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-3-methylthien-2-yl}-1-methyl-1H-1,2,4-triazole

[0342] Product was isolated as a clear oil (44% yield): ¹H NMR (CDCl₃) δ2.32 (s, 3H), 4.06 (s, 3H), 5.03 (m, 1H), 7.08-7.14 (m, 1H), 7.29-7.37(m, 4H), 7.39-7.44 (m, 3H); EI/MS 549 m/e (M+H); Calcd. forC₂₃H₁₅ClF₇N₃OS: C, 50.24; H, 2.75; N, 7.64; Found: C, 50.36; H, 3.01; N,7.39.

[0343]3-(2-Chloro-6-fluorophenyl)-5-(4-{4-[(2,2-dichloro-1-fluorovinyl)oxy]phenyl}-3-methylthien-2-yl)-1-methyl-1H-1,2,4-triazole

[0344] Product was isolated as a clear oil (10% yield): ¹H NMR (CDCl₃) δ2.31 (s, 3H), 4.06 (s, 3H), 7.08-7.17 (m, 3H), 7.29-7.37 (m, 2H),7.38-7.42 (m, 3H); EI/MS 512 m/e (M+H).

[0345]3-(2-Chloro-6-fluorophenyl)-5-{4-[4-(2,2-dichloro-1,1-difluoroethoxyphenyl]-3-methylthien-2-yl}-1-methyl-1H-1,2,4-triazole

[0346] Product was isolated as a white waxy solid (53% yield): mp114-116° C.; ¹H NMR (CDCl₃) δ 2.32 (s, 3H), 4.07 (s, 3H), 5.95 (t, 1H,J=4.8, 4.4 Hz), 7.08-7.14 (m, 1H), 7.28-7.38 (m, 4H), 7.39-7.42 (m, 3H);EI/MS 532 m/e (M+H).

Example 8

[0347]3-(2-Chloro-6-fluorophenyl)-5-[3-methyl-4-bromo-5-(4-trifluoromethoxyphenyl)-2-thienyl]-1-ethyl-[1,2,4]-triazole

[0348]Methyl-N-{[3-methyl-4-bromo-5-(4-trifluoromethoxyphenyl)-2-thienyl]-carbonyl}-2-fluoro-6-chlorobenzenecarbimidothioate(0.85 g, 1.5 mmol) and ethylhydrazine oxalate (0.90 g, 6 mmol) werecombined in toluene (5 mL) and stirred 64 h at 25° C. and heated toreflux for 18 h. The reaction mixture was diluted with ether and washedwith 0.1 M hydrochloric acid and brine, dried over anhydrous magnesiumsulfate and concentrated to a crude pale yellow oil. Chromatography(silica gel, 10% ethylacetate/hexane) afforded the product as a clearoil (0.250 mg, 30%): ¹H NMR (CDCl₃) δ 7.73 (2H, d), 7.0-7.5 (5H, m), 4.3(2H, q), 2.40 (3H, s), 1.55 (3H, t); EL/MS 546 m/e (M⁺).

Example 9

[0349]5-{5-Bromo-4-[4-(2-bromo-1,1,2-trifluoroethoxy)phenyl]-3-methylthien-2-yl}-3-(2-chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazole

[0350] Bromine (0.03 g, 0.2 mmol) in acetic acid (0.5 mL) was addeddropwise to a solution of5-{4-[4-(2-bromo-1,1,2-trifluoroethoxy)phenyl]-3-methylthien-2-yl}-3-(2-chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazole(0.1 g, 0.2 mmol) in acetic acid (1 mL) at 0° C. The reaction wasallowed to warm to 25° C. and stirred for 50 h. The reaction mixture wasmade basic with saturated aq NaHCO₃ (30 mL) and extracted with ether(3×30 mL). The combined ether extracts were washed with brine, driedover sodium sulfate, filtered, and the solvent removed under reducedpressure to give crude product. Column chromatography gave the productas a clear oil (88 mg, 77%): ¹H NMR (CDCl₃) δ 2.19 (s, 3H), 4.06 (s,3H), 6.58 (dt, 1H, J=47.6, 5.1, 4.0, 4.4 Hz), 7.08-7.14 (m, 1H),7.29-7.40 (m, 6H), EI/MS 636 m/e (M+H).

Example 10

[0351] The compounds identified in the following Tables 1-4 wereprepared using the procedures illustrated in the foregoing examples, andthe compounds were tested against tobacco budworm, beet armyworm,cabbage looper, cotton aphid, two-spotted spider mite, and sweetpotatowhitefly using procedures described hereinafter. TABLE 1

R¹ R² Y Ar TBW BAW CL CA SM WF Cl Cl Cl

G A E C G C Cl Cl Cl

B D F E G F Cl Cl Cl

G A A C G E Cl Cl Cl

G G D C A C CH₃ H Cl

D A B A A G CH₃ Br Cl

G A G A A G Cl H F

B A B F F G Cl H F

G A B G G G Cl H F

G B A D F G CH₃ H F

F A A A A F Cl H F

G A A G F G H Br Cl

G A A G A F Cl H Cl

A A A C A G Cl H Cl

A A A D A F Cl H Cl

G A D F G G Cl H Cl

G A D B A G Cl Br Cl

D B A A C F Cl H Cl

A A A B A G CH₃ H Cl

G A D B G F CH₃ H Cl

D A A A A D Cl Br Cl

F A A A G G Cl Br Cl

F D A A F G CH₃ H Cl

G D A B A G CH₃ H Cl

G G A B A F CH₃ H Cl

F D A B A G CH₃ H Cl

F D A A A A CH₃ H Cl

F A A C A G CH₃ H Cl

B A A A A G CH₃ H Cl

F A A C A G CH₃ H Cl

D A A D A G CH₃ H Cl

G A A B B G CH₃ H Cl

G B A D C G CH₃ H Cl

F F G B C G CH₃ H Cl

G D B D A CH₃ H Cl

A A A D A F CH₃ H Cl

A A A A B E CH₃ H Cl

A A A B A F Cl H Cl

A A A E C G

[0352] TABLE 2

R¹ R² Y Ar TBW BAW CL CA SM WF CH₃ H Cl

D A A A A A CH₃ H Cl

G D G A B G CH₃ H Cl

G B F A A F CH₃ H Cl

G B A B G A CH₃ H Cl

G D G B E G CH₃ H Cl

G D A A G G CH₃ H Cl

G B G B F CH₃ Br Cl

G A A B F D CH₃ CH₃ Cl

G A A A A E CH₃ Cl Cl

B A A C F G H H Cl

F A A D G G H H Cl

A A A F G G H H F

D G A A G G H Br Cl

B A A B A G CH₃ H Cl

G G B A G B H H F

G G A C G G H Br Cl

A A A G G G H H Cl

G F A A A G H CH₃ Cl

A A A A A G CH₃ H Cl

G G A A F B CH₃ H Cl

F A A A A A CH₃ H Cl

G A A A G A CH₃ H Cl

A A A B A A CH₃ H Cl

G G A A B A CH₃ H Cl

A A A D B A CH₃ H Cl

A A A B A A CH₃ H Cl

G A F A G A CH₃ H Cl

A A A B A A CH₃ H Cl

G G A B A G CH₃ H Cl

B A A A A G CH₃ H Cl

G G D C G F CH₃ H Cl

F D A A F F CH₃ H Cl

D G A A G G CH₃ H Cl

F G G A G G CH₃ H Cl

F A A A A A CH₃ H Cl

G B B C D F CH₃ H Cl

G D A B G G CH₃ H Cl

F G A B F F CH₃ H Cl

G G A A F E CH₃ H Cl

F G A A A G CH₃ H Cl

G F A A A G CH₃ H Cl

G G A B B F CH₃ H Cl

F G D B B F H H Cl

F G B G G H Cl Cl

G A A A A G H Cl Cl

A A A F A G H H Cl

D A A C C F H Cl Cl

F G A C G G H Cl Cl

G G A A A G H Cl Cl

G G B A G H H Cl

F G A B A F H Cl Cl

F A A F G F H CH₃ Cl

A A A F A G H CH₃ Cl

G A D B A C H Cl Cl

F A A F A F H Cl Cl

F A A F A H CH₃ Cl

G D G C A F H CH₃ Cl

G G A A A F H CH₃ Cl

G A A B A F H CH₃ Cl

F A A F A G H CH₃ Cl

G F A B G G CH₃ H Cl

B A A A F A CH₃ CH₃ Cl

D A A B F G CH₃ CH₃ Cl

G A A B H CH₃ Cl

G A A F B G H H Cl

G G F C F G CH₃ H Cl

G G A B F F H CH₃ Cl

F G G D G G CH₃ CH₃ Cl

G A A A C F CH₃ H Cl

A A A A A A Cl H Cl

B B A B C A Cl H Cl

A B A C C E CH₃ H Cl

G B A C E A CH₃ H F

G G A E G G Cl H Cl

F A A B A A CH₃ H Cl

A A A B F A CH₃ H Cl

A A A C B A CH₃ H Cl

F A F B F F CH₃ H Cl

A A A C E A CH₃ C₂H₅ Cl

B A A B G G CH₃ CH₃ Cl

A A A E G G CH₃ C₂H₅ Cl

F A A B G F

[0353] TABLE 3

R¹ R² Y Ar TBW BAW CL CA SM WF CH₃ H Cl

A A A A A A CH₃ H Cl

D D G D A F CH₃ Br Cl

G E G A G G CH₃ Cl Cl

G A G A G F CH₃ H Cl

E A A B A A CH₃ H Cl

B A A A G A CH₃ H Cl

B A A B C A CH₃ H Cl

A A A D A A CH₃ Br Cl

F A A B G F

[0354] TABLE 4

R¹ R² R³ Y Ar TBW BAW CL CA SM WF CH₃ Br Et Cl

G A A C C F

[0355] In each case the rating scale is as follows % Control Rating90-100 A 80-89 B 70-79 C 60-69 D 50-59 E less than 50 F Inactive G

[0356] Insecticide and Miticide Utility

[0357] The compounds of the invention are useful for the control ofinsects and mites. Therefore, the present invention also is directed toa method for inhibiting an insect or mite which comprises applying to alocus of the insect or mite an insect- or mite-inhibiting amount of acompound of formula (1).

[0358] The compounds are useful for reducing populations of insects andmites and are useful in a method of inhibiting an insect or mitepopulation which comprises applying to a locus of the insect or mite aneffective insect- or mite-inactivating amount of a compound of formula(1). The “locus” of insects or mites is a term used herein to refer tothe environment in which the insects or mites live or where their eggsare present, including the air surrounding them, the food they eat, orobjects which they contact. For example, insects or mites which eat orcontact edible or ornamental plants can be controlled by applying theactive compound to plant parts such as the seed, seedling, or cuttingwhich is planted, the leaves, stems, fruits, grain, or roots, or to thesoil in which the roots are growing. It is contemplated that thecompounds might also be useful to protect textiles, paper, stored grain,seeds, domesticated animals, buildings or human beings by applying anactive compound to or near such objects. The term “inhibiting an insector mite” refers to a decrease in the numbers of living insects or mites,or a decrease in the number of viable insect or mite eggs. The extent ofreduction accomplished by a compound depends, of course, upon theapplication rate of the compound, the particular compound used, and thetarget insect or mite species. At least an inactivating amount should beused. The terms “insect-inactivating amount” and “mite-inactivatingamount” are used to describe the amount, which is sufficient to cause ameasurable reduction in the treated insect or mite population. Generallyan amount in the range from about 1 to about 1000 ppm by weight activecompound is used. For example, insects and mites which” can be inhibitedinclude, but are not limited to:

[0359] Lepidoptera—Heliothis spp., Helicoverpa spp., Spodoptera spp.,Mythimna unipuncta, Agrotis ipsilon, Earias spp., Euxoa auxiliaris,Trichoplusia ni, Anticarsia gemmatalis, Rachiplusia nu, Plutellaxylostella, Chilo spp., Scirpophaga incertulas, Sesamia inferens,Cnaphalocrocis medinalis, Ostrinia nubilalis, Cydia pomonella, Carposinaniponensis, Adoxophyes orana, Archips argyrospilus, Pandemis heparana,Epinotia aporema, Eupoecilia ambiguella, Lobesia botrana, Polychrosisviteana, Pectinophora gossypiella, Pieris rapae, Phyllonorycter spp.,Leucoptera malifoliella, Phyllocnisitis citrella

[0360] Coleoptera—Diabrotica spp., Leptinotarsa decemlineata, Oulemaoryzae, Anthonomus grandis, Lissorhoptrus oryzophilus, Agriotes spp.,Melanotus communis, Popillia japonica, Cyclocephala spp., Tribolium spp.

[0361] Homoptera—Aphis spp., Myzus persicae, Rhopalosiphum spp.,Dysaphis plantaginea, Toxoptera spp., Macrosiphum euphorbiae,Aulacorthum solani, Sitobion avenae, Metopolophium dirhodum, Schizaphisgraminum, Brachycolus noxius, Nephotettix spp., Nilaparvata lugens,Sogatella furcifera, Laodelphax striatellus, Bemisia tabaci,Trialeurodes vaporariorum, Aleurodes proletella, Aleurothrixusfloccosus, Quadraspidiotus perniciosus, Unaspis yanonensis, Ceroplastesrubens, Aonidiella aurantii

[0362] Hemiptera—Lygus spp., Eurygaster maura, Nezara viridula,Piezodorus guildingi, Leptocorisa varicornis

[0363] Thysanoptera—Frankliniella occidentalis, Thrips spp.,Scirtothrips dorsalis

[0364] Isoptera—Reticulitermes flavipes, Coptotermes formosanus

[0365] Orthoptera—Blattella germanica, Blatta orientalis, Gryllotalpaspp.

[0366] Diptera—Liriomyza spp., Musca domestica, Aedes spp., Culex spp.,Anopheles spp.

[0367] Hymenoptera—Iridomyrmex humilis, Solenopsis spp., Monomoriumpharaonis, Atta spp., Pogonomyrmex spp., Camponotus spp.

[0368] Siphonaptera—Ctenophalides spp., Pulex irritans

[0369] Acarina—Tetranychus spp., Panonychus spp., Eotetranychus carpini,Phyllocoptruta oleivora, Aculus pelekassi, Brevipalpus phoenicis,Boophilus spp., Dermacentor variabilis, Rhipicephalus sanguineus,Amblyomma americanum, Ixodes spp., Notoedres cati, Sarcoptes scabiei,Dermatophagoides spp.

[0370] Insecticidal Test for Tobacco Budworm (Heliothis virescens) BeetArmyworm (Spodoptera exigua) and Cabbage Looper (Trichoplusia ni).

[0371] To prepare test solution, the test compound was formulated at 400ppm in 7.5 mL of 2 acetone: 1 tap water. 250 μL of the test solution waspipetted upon the surface of 8 mL of lepidopteran diet (modified Shorey)contained in each of five one-ounce plastic cups (one cup=1replication). A second-instar beet armyworm was placed upon the treateddiet in each cup once the solvent had air-dried. The solutions remainingafter completing applications to the one-ounce cups were then used asleaf-dip solutions for 3.5 cm leaf discs cut from cabbage leaves andcotton cotyledons. Five discs of each type of plant were dipped untilthoroughly coated into each rate of each compound (=5 replications ofeach treatment). After air-drying, the treated leaf discs were placedindividually into one-ounce plastic cups. Each dried, treated cottoncotyledon disc was infested with a 2^(nd) instar tobacco budworm larva,and each cabbage leaf disc was infested with a 2^(nd) instar cabbagelooper larva. Cups containing the treated substrates and larvae werecapped and then held in a growth chamber at 25° C., 50-55% RH, and 14 hrlight: 10 hr dark for 5 days. The number of dead insects of 5 perspecies per treatment was then determined and the results are given inTables 1-4.

[0372] Insecticidal Test for Cotton Aphid (Aphis gossypii)

[0373] To prepare spray solutions, 1 mg of each test compound wasdissolved into 1 mL of a 90:10 acetone:ethanol solvent. This 1 mL ofchemical solution was added to 19 mL of water containing 0.05% Tween 20surfactant to produce a 50 ppm spray solution.

[0374] Squash cotyledons were infested with cotton aphid (all lifestages)16-20 hours prior to application of spray solution. The solutionwas sprayed on both sides of each infested squash cotyledon (0.5 mL×2each side) with a sweeping action until runoff. The plants were allowedto air dry and held for 3 days in a controlled room at 26° C. and 40% RHafter which time the test was graded. Grading was by actual count usinga dissecting microscope and comparison of test counts to the untreatedcheck. Results are given in Tables 1-4 as percent control based onpopulation reduction versus the untreated.

[0375] Insecticidal Test for Two-Spotted Spider Mite (Tetranychusurticae)

[0376] Ovicide Method:

[0377] Ten adult female two-spotted spider mites were placed on eight2.2 cm leaf discs of cotton leaf, allowed to oviposit over 24 hours, andthereafter removed. The leaf discs were sprayed with 100 ppm testsolutions using a hand syringe, then allowed to dry with sixteen discsleft untreated as a negative control. Discs were placed on an agarsubstrate and held at 24° C. and 90% RH for 6 days. Percent controlbased on the number of hatched larvae on treated discs and the number onuntreated discs is reported in Tables 1-4.

[0378] Insecticidal Test for Sweetpotato Whitefly (Bemisia tabacia)

[0379] Four mg of each test compound was dissolved by adding 4 mL of a90:10 acetone:ethanol solvent mixture to the vial containing the samplecompound. This solution was added to 16 mL of water containing 0.05%Tween 20 surfactant to produce 20 mL of an 200 ppm spray solution.

[0380] Five-week-old cotton plants reared in a greenhouse were strippedof all foliage except for the two uppermost true leaves that weregreater than 5 cm in diameter. These plants were then placed into alaboratory colony of whiteflies for two days for oviposition by thecolony females. All whiteflies were then removed from the test plantswith pressurized air. The spray solution was then applied to the testplants with a hand-held syringe fitted with hollow cone nozzle. One mLspray solution was applied to each leaf top and bottom for a total of 4mL per plant. Four replications of each test compound utilized a totalof 16 mL spray solution. Plants were air dried and then placed in aholding chamber (28° C. and 60% RH) for 13 days. Compound efficacy wasevaluated by counting, under an illuminated magnifying glass, the numberof large nymphs (3rd-4th instar) per leaf.

[0381] Percent control based on reduction of large nymphs of a testcompound compared to solution-only (no test compound) sprayed plants isreported in Tables 1-4.

[0382] Compositions

[0383] The compounds of this invention are applied in the form ofcompositions which are important embodiments of the invention, and whichcomprise a compound of this invention and a phytologically-acceptableinert carrier. The compositions are either concentrated formulationswhich are dispersed in water for application, or are dust or granularformulations which are applied without further treatment. Thecompositions are prepared according to procedures and formulae which areconventional in the agricultural chemical art, but which are novel andimportant because of the presence therein of the compounds of thisinvention. Some description of the formulation of the compositions willbe given, however, to assure that agricultural chemists can readilyprepare any desired composition.

[0384] The dispersions in which the compounds are applied are most oftenaqueous suspensions or emulsions prepared from concentrated formulationsof the compounds. Such water-soluble, water-suspendable or emulsifiableformulations are either solids, usually known as wettable powders, orliquids usually known as emulsifiable concentrates or aqueoussuspensions. Wettable powders, which may be compacted to form waterdispersible granules, comprise an intimate mixture of the activecompound, an inert carrier, and surfactants. The concentration of theactive compound is usually from about 10% to about 90% by weight. Theinert carrier is usually chosen from among the attapulgite clays, themontmorillonite clays, the diatomaceous earths, or the purifiedsilicates. Effective surfactants, comprising from about 0.5% to about10% of the wettable powder, are found among the sulfonated lignins, thecondensed naphthalenesulfonates, the naphthalenesulfonates, thealkylbenzenesulfonates, the alkyl sulfates, and nonionic surfactantssuch as ethylene oxide adducts of alkyl phenols.

[0385] Emulsifiable concentrates of the compounds comprise a convenientconcentration of a compound, such as from about 50 to about 500 gramsper liter of liquid, equivalent to about 10% to about 50%, dissolved inan inert carrier which is either a water miscible solvent or a mixtureof water-immiscible organic solvent and emulsifiers. Useful organicsolvents include aromatics, especially the xylenes, and the petroleumfractions, especially the high-boiling naphthalenic and olefinicportions of petroleum such as heavy aromatic naphtha. Other organicsolvents may also be used, such as the terpenic solvents including rosinderivatives, aliphatic ketones such as cyclohexanone, and complexalcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiableconcentrates are chosen from conventional nonionic surfactants, such asthose discussed above.

[0386] Aqueous suspensions comprise suspensions of water-insolublecompounds of this invention, dispersed in an aqueous vehicle at aconcentration in the range from about 5% to about 50% by weight.Suspensions are prepared by finely grinding the compound, and vigorouslymixing it into a vehicle comprised of water and surfactants chosen fromthe same types discussed above. Inert ingredients, such as inorganicsalts and synthetic or natural gums, may also be added, to increase thedensity and viscosity of the aqueous vehicle. It is often most effectiveto grind and mix the compound at the same time by preparing the aqueousmixture, and homogenizing it in an implement such as a sand mill, ballmill, or piston-type homogenizer.

[0387] The compounds may also be applied as granular compositions, whichare particularly useful for applications to the soil. Granularcompositions usually contain from about 0.5% to about 10% by weight ofthe compound, dispersed in an inert carrier which consists entirely orin large part of clay or a similar inexpensive substance. Suchcompositions are usually prepared by dissolving the compound in asuitable solvent and applying it to a granular carrier which has beenpre-formed to the appropriate particle size, in the range of from about0.5 to 3 mm. Such compositions may also be formulated by making a doughor paste of the carrier and compound and crushing and drying to obtainthe desired granular particle size.

[0388] Dusts containing the compounds are prepared simply by intimatelymixing the compound in powdered form with a suitable dusty agriculturalcarrier, such as kaolin clay, ground volcanic rock, and the like. Dustscan suitably contain from about 1% to about 10% of the compound.

[0389] It is equally practical, when desirable for any reason, to applythe compound in the form of a solution in an appropriate organicsolvent, usually a bland petroleum oil, such as the spray oils, whichare widely used in agricultural chemistry.

[0390] Insecticides and acaricides are generally applied in the form ofa dispersion of the active ingredient in a liquid carrier. It isconventional to refer to application rates in terms of the concentrationof active ingredient in the carrier. The most widely used carrier iswater.

[0391] The compounds of the invention can also be applied in the form ofan aerosol composition. In such compositions the active compound isdissolved or dispersed in an inert carrier, which is apressure-generating propellant mixture. The aerosol composition ispackaged in a container from which the mixture is dispensed through anatomizing valve. Propellant mixtures comprise either low-boilinghalocarbons, which may be mixed with organic solvents, or aqueoussuspensions pressurized with inert gases or gaseous hydrocarbons.

[0392] The actual amount of compound to be applied to loci of insectsand mites is not critical and can readily be determined by those skilledin the art in view of the examples above. In general, concentrationsfrom 10 ppm to 5000 ppm by weight of compound are expected to providegood control. With many of the compounds, concentrations from 100 to1500 ppm will suffice.

[0393] The locus to which a compound is applied can be any locusinhabited by an insect or mite, for example, vegetable crops, fruit andnut trees, grape vines, ornamental plants, domesticated animals, theinterior or exterior surfaces of buildings, and the soil aroundbuildings.

[0394] Because of the unique ability of insect and mite eggs to resisttoxicant action, repeated applications may be desirable to control newlyemerged larvae, as is true of other known insecticides and acaricides.

We claim:
 1. A compound of the formula

wherein X and Y independently represent Cl or F; R¹ and R² independentlyrepresent H, C₁-C₆ alkyl or halogen, provided that R¹ and R² are notboth H; R³ represents C₁-C₃ alkyl; R⁴ represents halogen, C₁-C₆ alkyl,C₁-C₆ alkoxy, C₁-C₆ thioalkyl, C₃-C₆ alkoxyalkoxy, C₁-C₆ haloalkyl,C₁-C₆ haloalkoxy, C₁-C₆ halothioalkyl, C₃-C₆ alkenyloxy, or phenoxy; R⁵represents h, halogen or a c₁-C₆ alkyl ether or haloalkyl ether, which,when taken together with R⁴, form a 5- or 6-membered ring containing 1or 2 oxygen atoms; or a phytologically acceptable acid addition saltthereof.
 2. A compound of claim 1 in which R³ is CH₃.
 3. A compound ofclaim 1 in which X is F and Y is Cl.
 4. A compound of claim 1 in whichR¹ is CH₃.
 5. A compound of claim 1 in which R² is H or CH₃.
 6. Acompound of claim 1 in which R⁴ is F, Cl, CF₃, haloalkoxy or phenoxy. 7.A compound of claim 1 in which R⁵ is H, F, C₁ or CF₃.
 8. A compositionfor controlling lepidoptera, coleoptera, mites and other sucking pestswhich comprises a compound of the formula

wherein X and Y independently represent Cl or F; R¹ and R² independentlyrepresent H, C₁-C₆ alkyl or halogen, provided that R¹ and R² are notboth H; R³ represents C₁-C₃ alkyl; R⁴ represents halogen, C₁-C₆ alkyl,C₁-C₆ alkoxy, C₁-C₆ thioalkyl, C₃-C₆ alkoxyalkoxy, C₁-C₆ haloalkyl,C₁-C₆ haloalkoxy, C₁-C₆ halothioalkyl, C₃-C₆ alkenyloxy, or phenoxy; R⁵represents H, halogen or a C₁-C₆ alkyl ether or haloalkyl ether, which,when taken together with R⁴, form a 5- or 6-membered ring containing 1or 2 oxygen atoms; or a phytologically acceptable acid addition saltthereof in combination with a phytologically-acceptable carrier.
 9. Acomposition of claim 8 in which R³ is CH₃.
 10. A composition of claim 8in which X is F and Y is Cl.
 11. A composition of claim 8 in which R¹ isCH₃.
 12. A composition of claim 8 in which R² is H or CH₃.
 13. Acomposition of claim 8 in which R⁴ is F, Cl, CF₃, haloalkoxy or phenoxy.14. A composition of claim 8 in which R⁵ is H, F, C₁ or CF₃.
 15. Amethod of controlling lepidoptera, coleoptera, mites and other suckingpests which comprises applying to a locus where control is desired alepidoptera-, coleoptera-, mite- or other sucking pest-inactivatingamount of a compound of the formula

wherein X and Y independently represent Cl or F; R¹ and R² independentlyrepresent H, C₁-C₆ alkyl or halogen, provided that R¹ and R² are notboth H; R³ represents C₁-C₃ alkyl; R⁴ represents halogen, C₁-C₆ alkyl,C₁-C₆ alkoxy, C₁-C₆ thioalkyl, C₃-C₆ alkoxyalkoxy, C₁-C₆ haloalkyl,C₁-C₆ haloalkoxy, C₁-C₆ halothioalkyl, C₃-C₆ alkenyloxy, or phenoxy; R⁵represents H, halogen or a C₁-C₆ alkyl ether or haloalkyl ether, which,when taken together with R⁴, form a 5- or 6-membered ring containing 1or 2 oxygen atoms; or a phytologically acceptable acid addition saltthereof in combination with a phytologically-acceptable carrier.
 16. Amethod of claim 15 in which R³ is CH₃.
 17. A method of claim 15 in whichXmis F and Y is Cl.
 18. A method of claim 15 in which R¹ is CH₃.
 19. Amethod of claim 15 in which R² is H or CH₃.
 20. A method of claim 15 inwhich R⁴ is F, Cl, CF₃, haloalkoxy or phenoxy.
 21. A method of claim 15in which R⁵ is H, F, C₁ or CF₃.